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Sample records for lymphoid organs hepatopathy

  1. Innate lymphoid cells in secondary lymphoid organs.

    Science.gov (United States)

    Bar-Ephraïm, Yotam E; Mebius, Reina E

    2016-05-01

    The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper-like ILCs with functional distinctions as seen by T-helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology.

  2. Bioengineering of Artificial Lymphoid Organs

    OpenAIRE

    Nosenko, M. A.; Drutskaya, M. S; M. M. Moisenovich; Nedospasov, S A

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cy...

  3. Bioengineering of Artificial Lymphoid Organs.

    Science.gov (United States)

    Nosenko, M A; Drutskaya, M S; Moisenovich, M M; Nedospasov, S A

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cytokine signaling pathways regulating these processes. We describe various polymeric materials, as scaffolds, for artificial tissue engineering. Finally, published studies in which artificial lymphoid organs were generated are reviewed and possible future directions in the field are discussed.

  4. Schistosomal hepatopathy

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    Zilton A Andrade

    2004-08-01

    Full Text Available Gross anatomical features and a complex set of vascular changes characterize schistosomal hepatopathy as a peculiar form of chronic liver disease, clinically known as "hepatosplenic schistosomiasis". It differs from hepatic cirrhosis, although clinical and pathological aspects may sometimes induce confusion between these two conditions. Intrahepatic portal vein obstruction and compensatory arterial hypertrophy render the hepatic parenchyma vulnerable to ischemic insult. This may lead to focal necrosis, which may give place to focal post-necrotic scars. These events are of paramount importance for the clinico-pathological evolution of schistosomal hepatopathy. Although portal fibrosis due to schistosomiasis sometimes reveals numerous myofibroblasts, it does not mean that such fibrosis belongs to a peculiar type. Damage to the muscular walls of the portal vein may be followed by dissociation of smooth muscle cells and their transition toward myofibroblasts, which appear only as transient cells in schistosomal portal fibrosis. Studies made with plastic vascular casts, especially those with the murine model of "pipestem" fibrosis have helped to reveal the mechanisms involved in systematized portal fibrosis formation. However, the factors involved in the pathogenesis of hepatosplenic disease remain poorly understood. A process of chronic hepatitis is a common accompaniment of portal fibrosis in schistosomiasis. Most of the times it is caused by concomitant viral infection. However, no especial interaction seems to exist between schistosomal hepatopathy and viral hepatitis.

  5. Effect of Copper Toxicity on Lymphoid Organs in Ducklings

    Institute of Scientific and Technical Information of China (English)

    CUI Heng-min; CHEN Huai-tao; PENG Xi; YANG Guang; DENG Jun-liang; LI De-bing

    2004-01-01

    210 one-day-old Tianfu meat ducklings ware divided into three groups,and fed on diets as follows: (1) control (Cu 12.16 mg kg-1),(2) copper toxic Ⅰ (Cu 850 mg kg-1) and (3)copper toxic Ⅱ( Cu 1 050 mg kg-1) for studies on effects of copper toxicity on lymphoid organs in duckling with the methods of experimental pathology and flow cytometry (FCM).The weight and growth index of the thymus,spleen and bursa of Fabricius were markedly reduced (P< 0.05 or P< 0.01) in both copper toxic group Ⅰ and Cu toxic group Ⅱ when compared with control group.The G0/G1 phase of the cell cycle of the thymus,spleen and bursa of Fabricius was much higher,and S,G2+M phases lower in Cu toxic groups Ⅰ and Ⅱ than in the control group.There were lymphocyte degeneration and depletion of lymphoid organs,and the reticular cells of spleen and bursa of Fabricius proliferated and the reticular cells of thymus were also degenerate and necrotic in Cu toxic groups.The results demonstrated that Cu toxicity seriously impaired the progression of lymphocytes from the G0/G1 phase to S phase,inhibited the development of lymphoid organs and caused marked pathological injury in lymphoid organs.The results also showed that the effect of Cu toxicity on the primary lymphoid organs occurred stronger than on the secondary lymphoid organs.The effect of Cu toxicity was the greatest on the bursa of Fabricius,followed hy the thymus,and then the spleen.Potential mechanisms underlying aforementioned observation were also discussed.key words: Copper toxicity,Lesion,Cell cycle,Lymphoid organ,Duckling

  6. Effect of Zinc Toxicity on Lymphoid Organs in Chickens

    Institute of Scientific and Technical Information of China (English)

    CUI Heng-min; ZHAO Cui-yan; LI De-bing; PENG Xi; DENG Jun-liang

    2004-01-01

    The experiment was conducted with the objective of studies on effects of zinc toxicity on lymphoid organs by the methods of experimental pathology and flow cytometry (FCM). 200one-day-old Avian broilers were divided into four groups randomly, and fed on diets as follows: controls (Zn 100mg kg-1)and zinc toxic (Zn 1 500mg kg-1, zinc toxic group Ⅰ; Zn 2 000 mg kg-1, zinc toxic group Ⅱ; Zn 2 500 mg kg-1, zinc toxic group Ⅲ) for seven weeks. The weight and growth index of the thymus, spleen and bursa of Fabricius were reduced in both zinc toxic group Ⅱ and zinc toxic group Ⅲ when compared with those of control group. The G0/G1 phase of the cell cycles of the lymphoid organs was higher, and S, G2+M phases lower in zinc toxic groups Ⅱ and Ⅲ than in control group. Lymphocytes were depleted and degenerate in the lymphoid organs. The reticular cells of the bursa of Fabricius proliferated and the reticular cells of the thymus were also degenerate and necrotic,particularly in zinc toxic groups Ⅱ and Ⅲ. The results demonstrated that more than 1 500 mg kg-1 impaired the progression of lymphocytes from the G0/G1 phase to S phase obviously, inhibited the development of lymphoid organs and caused marked pathological changes in the lymphoid organs. Potential mechanisms underlying these observations are also discussed.

  7. THE EXTENT OF CLONAL STRUCTURE IN DIFFERENT LYMPHOID ORGANS

    NARCIS (Netherlands)

    HERMANS, MHA; WUBBENA, A; KROESE, FGM; HUNT, SV; COWAN, R; OPSTELTEN, D

    1992-01-01

    To gain insight into the clonal organization of lymphoid organs, we studied the distribution in situ of donor-derived cells in near-physiological chimeras. We introduced RT7b fetal liver cells into nonirradiated congenic RT7a neonatal rats. The chimerism 6-20 wk after injection ranged from 0.3 to 20

  8. [Meningeal tertiary lymphoid organs: Major actors in intrathecal autoimmunity].

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    Bonnan, M

    2015-01-01

    Multiple sclerosis (MS) is characterized by an intrathecal synthesis of immunoglobulins synthesized by B-cell clones and by a brain infiltrate of clonal T-cells. The clonal maturation of these lymphocytes takes place in tertiary lymphoid organs (TLO) developed in the intrathecal compartment. TLO are acquired lymphoid organs able to develop in the vicinity of the inflammatory sites, where they mount a complete antigen-driven immune response. We here review TLO pathophysiology in animal models of MS and human MS. Several pieces of evidence suggest that intrathecal TLO may play a major role in the clinical impairment. Potential therapeutic applications are examined.

  9. Human Ia-like antigens in non-lymphoid organs.

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    Koyama, K; Fukunishi, T; Barcos, M; Tanigaki, N; Pressman, D

    1979-01-01

    Human Ia-like antigens in liver and kidney were shown by the immunofluorescence assay to be present mostly in the endothelial-mesenchymal cells of these organs. The parenchymal cells apparently contained no human Ia-like antigens. The antigens in liver and kidney were purified and shown to have the same subunit structure as human Ia-like antigens of cultured B-lymphoid cells. The human Ia-like antigens in non-lymphoid organs, not only in liver and kidney but also in testis, heart, muscle and brain, carried all the xenoantigenic characteristics of human Ia-like antigens expressed on lymphoid cells of B-cell lineage. Images Figure 1 PMID:389786

  10. Avian dendritic cells: Phenotype and ontogeny in lymphoid organs.

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    Nagy, Nándor; Bódi, Ildikó; Oláh, Imre

    2016-05-01

    Dendritic cells (DC) are critically important accessory cells in the innate and adaptive immune systems. Avian DCs were originally identified in primary and secondary lymphoid organs by their typical morphology, displaying long cell processes with cytoplasmic granules. Several subtypes are known. Bursal secretory dendritic cells (BSDC) are elongated cells which express vimentin intermediate filaments, MHC II molecules, macrophage colony-stimulating factor 1 receptor (CSF1R), and produce 74.3+ secretory granules. Avian follicular dendritic cells (FDC) highly resemble BSDC, express the CD83, 74.3 and CSF1R molecules, and present antigen in germinal centers. Thymic dendritic cells (TDC), which express 74.3 and CD83, are concentrated in thymic medulla while interdigitating DC are found in T cell-rich areas of secondary lymphoid organs. Avian Langerhans cells are a specialized 74.3-/MHC II+ cell population found in stratified squamous epithelium and are capable of differentiating into 74.3+ migratory DCs. During organogenesis hematopoietic precursors of DC colonize the developing lymphoid organ primordia prior to immigration of lymphoid precursor cells. This review summarizes our current understanding of the ontogeny, cytoarchitecture, and immunophenotype of avian DC, and offers an antibody panel for the in vitro and in vivo identification of these heterogeneous cell types.

  11. Impaired Lymphoid Organ Development in Mice Lacking the Heparan Sulfate Modifying Enzyme Glucuronyl C5-Epimerase

    NARCIS (Netherlands)

    R.M. Reijmers; M.F.R. Vondenhoff; R. Roozendaal; A. Kuil; J.P. Li; M. Spaargaren; S.T. Pals; R.E. Mebius

    2010-01-01

    The development of lymphoid organs depends on cross talk between hematopoietic cells and mesenchymal stromal cells and on vascularization of the lymphoid primordia. These processes are orchestrated by cytokines, chemokines, and angiogenic factors that require tight spatiotemporal regulation. Heparan

  12. Fibroblasts as Efficient Antigen-Presenting Cells in Lymphoid Organs

    Science.gov (United States)

    Kundig, Thomas M.; Bachmann, Martin F.; Dipaolo, Claudio; Simard, John J. L.; Battegay, Manuel; Lother, Heinz; Gessner, Andre; Kuhlcke, Klaus; Ohashi, Pamela S.; Hengartner, Hans; Zinkernagel, Rolf M.

    1995-06-01

    Only so-called "professional" antigen-presenting cells (APCs) of hematopoietic origin are believed capable of inducing T lymphocyte responses. However, fibroblasts transfected with viral proteins directly induced antiviral cytotoxic T lymphocyte responses in vivo, without involvement of host APCs. Fibroblasts induced T cells only in the milieu of lymphoid organs. Thus, antigen localization affects self-nonself discrimination and cell-based vaccine strategies.

  13. Ontogeny of the Lymphoid Organs of Japanese Flounder, Paralichthys olivaceus

    Institute of Scientific and Technical Information of China (English)

    LIU Yun; JIANG Guoliang; ZHANG Shicui

    2004-01-01

    Histological study on the ontogeny of the lymphoid organs, kidney, thymus and spleen of Japanese flounder, Paralichthys olivaceus, from hatching to 40 d was carried out. The pronephric kidney duct appeared early in hatching although the primordial haemopoietic stem cells were observed within a week after hatching. The spleen was first seen after 8 d of hatching. The thymus appeared after 15 d, situated near the pronephric kidney. Small lymphoid cells appeared during the later phase of the post-larval stage in the sequence of thymus, kidney and spleen. During the 40 d of observations, there were no distinct inner or outer zones in thymus and no red or white pulp in spleen. These results suggest that the nonspecific defense immune system plays a very important role in the early larval stage of Japanese flounder.

  14. Inducers & Organizers in Human Fetal and Adult Lymphoid Tissues : the characterization of RORC+ innate lymphoid cells and RANKL+ marginal reticular cells in human fetal and adult secondary lymphoid organs

    NARCIS (Netherlands)

    K. Hoorweg (Kerim)

    2014-01-01

    markdownabstract__Abstract__ The human immune system harbors the potential to generate novel lymphoid organs within inflamed tissues during disease. These tertiary lymphoid organs (TLOs) resemble lymph nodes and can contain segregated T and B cell areas, germinal centers, high endothelial venules a

  15. Effect of Copper Toxicity on Lymphoid Organs in Broilers

    Institute of Scientific and Technical Information of China (English)

    CUI Heng-min; YANG Guang; PENG Xi; DENG Jun-liang; LI De-bing

    2005-01-01

    The experiment was conducted to examine the effect of copper toxicity on lymphoid organs by experimental pathology and flow cytometry (FCM). 180 one-day-old Avian broilers were divided into three groups, and fed diets as follows: 1) Control(Cu 11.97 mg kg-1 diet), 2) Cu- toxic group Ⅰ (Cu 650 mg kg-1) and 3) Cu- toxic group Ⅱ (Cu 850 mg kg-1) for six weeks.Compared with the control, the growth index of the thymus, spleen and bursa of Fabricius were markedly reduced (P<0.05or P<0.01), the G0/G1 phase of cell cycles of the thymus, spleen and bursa of Fabricius was higher (P<0.05 or P<0.01), while the S phase and proliferating index were lower (P<0.05 or P<0.01)in both Cu-toxic group Ⅰ and Cu-toxic group Ⅱ. The results demonstrated that Cu toxicity seriously impaired the progression of lymphocytes from the G0/G1 phase to the S phase, inhibited the growth and development of lymphoid organs.

  16. Lymphoid organ-resident dendritic cells exhibit unique transcriptional fingerprints based on subset and site.

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    Kutlu G Elpek

    Full Text Available Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions.

  17. Prions and lymphoid organs: solved and remaining mysteries.

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    O'Connor, Tracy; Aguzzi, Adriano

    2013-01-01

    Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1 (-/-) lymph nodes and rates of neuroinvasion in TNFR1 (-/-) mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1 (-/-) lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)-the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article.

  18. Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

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    Meike Mitsdoerffer

    2016-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS, which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease, however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function and clinical significance. Mechanistic studies in patiens are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs.

  19. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon

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    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID

  20. Malarial hepatopathy and its outcome in India

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    Rama Prakasha Saya

    2012-01-01

    Full Text Available Background: Jaundice in Plasmodium falciparum malaria is multifactorial and its incidence varies in different regions. It is important to assess the incidence and factors associated with malarial hepatopathy as well as its complications to understand the pattern of disease presentation in order to undertake appropriate interventional measures. There is a paucity of data with regard to malarial hepatopathy and its outcome at the global level. Aim: The study was conducted to assess the pattern, spectrum of biochemical parameters and complications of hepatopathy related to P. falciparum malaria. Materials and Methods: A descriptive study was conducted in a tertiary care hospital attached to a government medical institution in Assam, India. Demographic details of the hundred patients with P. falciparum malaria, their clinical and biochemical parameters, complications and outcome were collected using a prestructured proforma. Data was compared using proportion and Chi Square test. Results: The proportion of those with malarial hepatopathy was 38% and the incidence was more in males and younger age group. The degree of hyperbilirubinemia, complications that include renal failure, shock, acute respiratory distress syndrome, hypoglycemia and mortality were significantly more among patients with hepatopathy (P<0.05. Conclusion: Malarial hepatopathy is associated with a higher incidence of complications like renal failure, shock, acute respiratory distress syndrome and hypoglycemia. Further studies are required to elucidate the factors associated with malarial hepatopathy and to prevent the complications and mortality.

  1. Stromal cells in chronic inflammation and tertiary lymphoid organ formation.

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    Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge

    2015-01-01

    Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

  2. Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing.

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    Nikolich-Žugich, J; Davies, J S

    2017-03-01

    Ageing of the innate and adaptive immune system, collectively termed immune senescence, is a complex process. One method to understand the components of ageing involves dissociating the effects of ageing on the cells of the immune system, on the microenvironment in lymphoid organs and tissues where immune cells reside and on the circulating factors that interact with both immune cells and their microenvironment. Heterochronic parabiosis, a surgical union of two organisms of disparate ages, is ideal for this type of study, as it has the power to dissociate the age of the cell and the age of the microenvironment into which the cell resides or is migrating. So far, however, it has been used sparingly to study immune ageing. Here we review the limited literature on homeostatic innate immune cell trafficking in ageing in the absence of chronic inflammation. We also review our own recent data on trafficking of innate immune subsets between primary and secondary lymphoid organs in heterochronic parabiosis. We found no systemic bias in retention or acceptance of neutrophils, macrophages, dendritic cells or natural killer cells with ageing in primary and secondary lymphoid organs. We conclude that these four innate immune cell types migrate to and populate lymphoid organs (peripheral lymph nodes, spleen and bone marrow), regardless of their own age and of the age of lymphoid organs. © 2017 British Society for Immunology.

  3. Human secondary lymphoid organs typically contain polyclonally-activated proliferating regulatory T cells.

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    Peters, Jorieke H; Koenen, Hans J P M; Fasse, Esther; Tijssen, Henk J; Ijzermans, Jan N M; Groenen, Patricia J T A; Schaap, Nicolaas P M; Kwekkeboom, Jaap; Joosten, Irma

    2013-09-26

    Immunomodulating regulatory T-cell (Treg) therapy is a promising strategy in autoimmunity and transplantation. However, to achieve full clinical efficacy, better understanding of in vivo human Treg biology is warranted. Here, we demonstrate that in contrast to blood and bone marrow Tregs, which showed a resting phenotype, the majority of CD4(pos)CD25(pos)CD127(neg)FoxP3(pos) Tregs in secondary lymphoid organs were proliferating activated CD69(pos)CD45RA(neg) cells with a hyperdemethylated FOXP3 gene and a broad T-cell receptor-Vβ repertoire, implying polyclonal activation. Activated CD69(pos) Tregs were distributed over both T-cell and B-cell areas, distant from Aire(pos) and CD11c(pos) cells. In contrast to the anergic peripheral blood Tregs, lymphoid organ Tregs had significant ex vivo proliferative capacity and produced cytokines like interleukin-2, while revealing similar suppressive potential. Also, next to Treg-expressing chemokine receptors important for a prolonged stay in lymphoid organs, a significant part of the cells expressed peripheral tissue-associated, functional homing markers. In conclusion, our data suggest that human secondary lymphoid organs aid in the maintenance and regulation of Treg function and homeostasis. This knowledge may be exploited for further optimization of Treg immunotherapy, for example, by ex vivo selection of Tregs with capacity to migrate to lymphoid organs providing an in vivo platform for further Treg expansion.

  4. [Insulin, peptide C and glucide tolerance in chronic alcoholic hepatopathies].

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    Nardoni, A; Marchetti, E; Sabattini, E; Geatti, O; Nador, G

    1984-09-08

    Changes in blood glucose and insulin metabolism, both under basal conditions and after glucose and glucagon stimulus, were studied in 95 patients with chronic alcoholic hepatopathy. Peptide C was also determined in 19 patients. A high incidence of islet-cell insufficiency was noted. Stress is laid on the multiplicity of the pathogenetic mechanisms responsible for blood glucose and insulin changes during chronic alcoholic hepatopathy, particularly liver cell damage, hyperglucagonaemia, organic and/or functional islet-cell insufficiency, and peripheral insulin resistance. It is felt that the last two of these are of major importance, whereas liver cell damage is of secondary significance, at any rate as far as glucose and insulin turnover is concerned.

  5. Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together

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    Jones, Gareth W.; Hill, David G.; Jones, Simon A.

    2016-01-01

    Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules. In this respect, they mimic the activities of germinal centers and contribute to the local control of adaptive immune responses. Studies in various disease settings have described how these structures contribute to either beneficial or deleterious outcomes. While the development and architectural organization of TLOs within inflamed tissues requires homeostatic chemokines, lymphoid and inflammatory cytokines, and adhesion molecules, our understanding of the cells responsible for triggering these events is still evolving. Over the past 10–15 years, novel immune cell subsets have been discovered that have more recently been implicated in the control of TLO development and function. In this review, we will discuss the contribution of these cell types and consider the potential to develop new therapeutic strategies that target TLOs.

  6. Multispectral imaging reveals the tissue distribution of tetraspanins in human lymphoid organs.

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    de Winde, Charlotte M; Zuidscherwoude, Malou; Vasaturo, Angela; van der Schaaf, Alie; Figdor, Carl G; van Spriel, Annemiek B

    2015-08-01

    Multispectral imaging is a novel microscopy technique that combines imaging with spectroscopy to obtain both quantitative expression data and tissue distribution of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane proteins involved in cellular and humoral immune responses. However, comprehensive immunohistochemical analyses of CD37 and CD53 in human lymphoid organs have not been performed so far. We investigated CD37 and CD53 protein expression on primary human immune cell subsets in blood and in primary and secondary lymphoid organs. Both tetraspanins were prominently expressed on antigen-presenting cells, with highest expression of CD37 on B lymphocytes. Analysis of subcellular distribution showed presence of both tetraspanins on the plasma membrane and on endosomes. In addition, CD53 was also present on lysosomes. Quantitative analysis of expression and localization of CD37 and CD53 on lymphocytes within lymphoid tissues by multispectral imaging revealed high expression of both tetraspanins on CD20(+) cells in B cell follicles in human spleen and appendix. CD3(+) T cells within splenic T cell zones expressed lower levels of CD37 and CD53 compared to T cells in the red pulp of human spleen. B cells in human bone marrow highly expressed CD37, whereas the expression of CD53 was low. In conclusion, we demonstrate differential expression of CD37 and CD53 on primary human immune cells, their subcellular localization and their quantitative distribution in human lymphoid organs. This study provides a solid basis for better insight into the function of tetraspanins in the human immune response.

  7. CollagenVI-Cre mice: A new tool to target stromal cells in secondary lymphoid organs.

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    Prados, Alejandro; Kollias, George; Koliaraki, Vasiliki

    2016-09-08

    Stromal cells in secondary lymphoid organs (SLOs) are non-hematopoietic cells involved in the regulation of adaptive immune responses. Three major stromal populations have been identified in adult SLOs: fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs) and marginal reticular cells (MRCs). The properties of these individual populations are not clearly defined, mainly due to the lack of appropriate genetic tools, especially for MRCs. Here, we analyzed stromal cell targeting in SLOs from a transgenic mouse strain that expresses Cre recombinase under the CollagenVI promoter, using lineage tracing approaches. We show that these mice target specifically MRCs and FDCs, but not FRCs in Peyer's patches and isolated lymphoid follicles in the intestine. In contrast, stromal cells in lymph nodes and the spleen do not express the transgene, which renders ColVI-cre mice ideal for the specific targeting of stromal cells in the gut-associated lymphoid tissue (GALT). This funding further supports the hypothesis of organ-specific stromal precursors in SLOs. Interestingly, in all tissues analyzed, there was also high specificity for perivascular cells, which have been proposed to act as FDC precursors. Taken together, ColVI-Cre mice are a useful new tool for the dissection of MRC- and FDC-specific functions and plasticity in the GALT.

  8. Local glucocorticoid production in lymphoid organs of mice and birds: Functions in lymphocyte development.

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    Taves, Matthew D; Hamden, Jordan E; Soma, Kiran K

    2017-02-01

    Circulating glucocorticoids (GCs) are powerful regulators of immunity. Stress-induced GC secretion by the adrenal glands initially enhances and later suppresses the immune response. GC targets include lymphocytes of the adaptive immune system, which are well known for their sensitivity to GCs. Less appreciated, however, is that GCs are locally produced in lymphoid organs, such as the thymus, where GCs play a critical role in selection of the T cell antigen receptor (TCR) repertoire. Here, we review the roles of systemic and locally-produced GCs in T lymphocyte development, which has been studied primarily in laboratory mice. By antagonizing TCR signaling in developing T cells, thymus-derived GCs promote selection of T cells with stronger TCR signaling. This results in increased T cell-mediated immune responses to a range of antigens. We then compare local and systemic GC patterns in mice to those in several bird species. Taken together, these studies suggest that a combination of adrenal and lymphoid GC production might function to adaptively regulate lymphocyte development and selection, and thus antigen-specific immune reactivity, to optimize survival under different environmental conditions. Future studies should examine how lymphoid GC patterns vary across other vertebrates, how GCs function in B lymphocyte development in the bone marrow, spleen, and the avian bursa of Fabricius, and whether GCs adaptively program immunity in free-living animals.

  9. Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs.

    Science.gov (United States)

    Washio, Ken; Kotani, Takenori; Saito, Yasuyuki; Respatika, Datu; Murata, Yoji; Kaneko, Yoriaki; Okazawa, Hideki; Ohnishi, Hiroshi; Fukunaga, Atsushi; Nishigori, Chikako; Matozaki, Takashi

    2015-06-01

    Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell-cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c(+) DCs (Sirpa(Δ) (DC) ). Sirpa(Δ) (DC) mice manifested a marked reduction of CD4(+) CD8α(-) conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa(Δ) (DC) mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell-selective adhesion molecule (ESAM) or Epstein-Barr virus-induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM(+) or EBI2(+) cDCs were markedly reduced in the spleen of Sirpa(Δ) (DC) mice. Thus, our results suggest that SIRPα intrinsic to CD11c(+) DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.

  10. Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response.

    Science.gov (United States)

    Kuerten, Stefanie; Schickel, Achim; Kerkloh, Christian; Recks, Mascha S; Addicks, Klaus; Ruddle, Nancy H; Lehmann, Paul V

    2012-12-01

    While the role of T cells has been studied extensively in multiple sclerosis (MS), the pathogenic contribution of B cells has only recently attracted major attention, when it was shown that B cell aggregates can develop in the meninges of a subset of MS patients and were suggested to be correlates of late-stage and more aggressive disease in this patient population. However, whether these aggregates actually exist has subsequently been questioned and their functional significance has remained unclear. Here, we studied myelin basic protein (MBP)-proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE), which is one of the few animal models for MS that is dependent on B cells. We provide evidence that B cell aggregation is reflective of lymphoid neogenesis in the central nervous system (CNS) in MBP-PLP-elicited EAE. B cell aggregation was present already few days after disease onset. With disease progression CNS B cell aggregates increasingly displayed the phenotype of tertiary lymphoid organs (TLOs). Our results further imply that these TLOs were not merely epiphenomena of the disease, but functionally active, supporting intrathecal determinant spreading of the myelin-specific T cell response. Our data suggest that the CNS is not a passive "immune-privileged" target organ, but rather a compartment, in which highly active immune responses can perpetuate and amplify the autoimmune pathology and thereby autonomously contribute to disease progression.

  11. Eye extract improves cell migration out of lymphoid organ explants of L. vannamei and viability of the primary cell cultures.

    Science.gov (United States)

    Li, Wenfeng; Van Tuan, Vo; Van Thuong, Khuong; Bossier, Peter; Nauwynck, Hans

    2015-08-01

    Since no cell line from shrimp has been established up till now, an optimization of the primary cell culture protocol is necessary. In this context, the effect of extracts (supernatant of a 1:50 (w/v) suspension) from different shrimp organs (muscle, brain, ganglia, eyestalk, ovary, and eye) on the performance of primary lymphoid cell cultures was evaluated. Ten percent of eye extract and 3% of ovary extract enhanced maximally the migration and survival of cells of the lymphoid organ of Litopenaeus vannamei significantly at 48, 96, and 144 h post seeding. Extracts from the eyestalk (10%), muscle (10%), and brain (1%) significantly promoted the migration and survival of cells at 48 and 96 h post seeding but not anymore at 144 h post seeding. In conclusion, it may be advised to add 10% of eye extract or 3% of ovary extract to cells for the maximal health of primary cell cultures from the lymphoid organ of L. vannamei.

  12. Follicular dendritic cells, conduits, lymphatic vessels, and high endothelial venules in tertiary lymphoid organs: Parallels with lymph node stroma

    Directory of Open Access Journals (Sweden)

    Sharon eStranford

    2012-11-01

    Full Text Available In this communication, the contribution of stromal, or non-hematopoietic, cells to the structure and function of lymph nodes (LNs, as canonical secondary lymphoid organs (SLOs, is compared to that of tertiary lymphoid tissue or organs (TLOs, also known as ectopic lymphoid tissues. TLOs can arise in non-lymphoid organs during chronic inflammation, as a result of autoimmune responses, graft rejection, atherosclerosis, microbial infection, and cancer. The stromal components found in SLOs including follicular dendritic cells, fibroblast reticular cells, lymphatic vessels, and high endothelial venules and possibly conduits are present in TLOs; their molecular regulation mimics that of LNs. Advances in visualization techniques and the development of transgenic mice that permit in vivo real time imaging of these structures will facilitate elucidation of their precise functions in the context of chronic inflammation. A clearer understanding of the inflammatory signals that drive non lymphoid stromal cells to reorganize into TLOs could allow the design of therapeutic interventions to impede the progression of autoimmune activity, or alternatively, to enhance anti-tumor responses.

  13. Choreography of cell motility and interaction dynamics imaged by two-photon microscopy in lymphoid organs.

    Science.gov (United States)

    Cahalan, Michael D; Parker, Ian

    2008-01-01

    The immune system is the most diffuse cellular system in the body. Accordingly, long-range migration of cells and short-range communication by local chemical signaling and by cell-cell contacts are vital to the control of an immune response. Cellular homing and migration within lymphoid organs, antigen recognition, and cell signaling and activation are clearly vital during an immune response, but these events had not been directly observed in vivo until recently. Introduced to the field of immunology in 2002, two-photon microscopy is the method of choice for visualizing living cells deep within native tissue environments, and it is now revealing an elegant cellular choreography that underlies the adaptive immune response to antigen challenge. We review cellular dynamics and molecular factors that contribute to basal motility of lymphocytes in the lymph node and cellular interactions leading to antigen capture and recognition, T cell activation, B cell activation, cytolytic effector function, and antibody production.

  14. Effects of various kinds of edible seaweeds in diets on the development of D-galactosamine-induced hepatopathy in rats.

    Science.gov (United States)

    Kawano, Naoko; Egashira, Yukari; Sanada, Hiroo

    2007-08-01

    In the present study we investigated the effects of 11 kinds of edible seaweeds (6 brown and 5 red algae) which contain characteristic seaweed dietary fibers on the induction of D-GalN (D-galactosamine)-hepatopathy in rats (Exps. 1 and 2). Then, the efficacy of various components prepared from Gelidium sp., which was found to alleviate the hepatopathy in Exps. 1 and 2, was examined (Exp. 3). The rats were fed the diets containing various kinds of seaweeds (Exps. 1 and 2), or several components of Gelidium sp. such as total dietary fiber (TDF), soluble dietary fiber (SDF), insoluble dietary fiber (IDF) and dietary fiber-free components (DFFC) (Exp. 3), for 8 d. The rats in all experiments were injected with D-GalN (800 mg/kg body weight) intraperitoneally at the 7th day to induce liver injury and were sacrificed 24 h after the injection of D-GalN. The serum transaminase activities (ALT and AST) and lactate dehydrogenase (LDH) were determined to evaluate the levels of hepatopathy. In Exp. 3, the total GSH concentration in the liver, plasma and cecal contents and organic acid concentration in cecal contents were also evaluated. In Exps. 1 and 2, repressive effects against D-GalN-hepatopathy were shown by four seaweeds Laminaria sp., Gelidium sp., Sargassum fulvellum and Eisenia bicyclis. In Exp. 3, it was found that protective activity in Gelidium sp. against D-GalN-hepatopathy existed not only in the SDF but also in the DFFC fraction. The results in Exp. 3 also indicated that the total GSH but not organic acid concentration in the cecal contents were significantly correlated with serum AST activity, suggesting that the protective effect of Gelidium sp. on D-GalN-hepatopathy in rats is related to GSH metabolism in the intestine.

  15. Effects of xenogeneic, allogeneic and isogeneic thymus grafts on lymphocyte populations in peripheral lymphoid organs of the nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B; Stenvang, J P

    1987-01-01

    In order to gain information about the effect of xenografted, allografted and isografted thymic tissue on peripheral lymphoid organs of immune-deficient rats, athymic nude LEW rats of ninth backcross-intercross were grafted with fetal calf and neonatal BDIX and LEW thymus. Adrenalectomy was also...

  16. Comparing CDRH3 diversity captured from secondary lymphoid organs for the generation of recombinant human antibodies.

    Science.gov (United States)

    Venet, Sophie; Kosco-Vilbois, Marie; Fischer, Nicolas

    2013-01-01

    The plasticity of natural immunoglobulin repertoires can be exploited for the generation of phage display libraries. Secondary lymphoid organs, such as the spleen and the lymph nodes, constitute interesting sources of diversity because they are rich in B cells, part of which can be affinity matured. These organs, however, differ in their anatomical structure, reflecting the different fluids they drain, which affects the B cell repertoires. The CDRH3 repertoires from these organs, extracted from naïve or immunized mice, were compared in the context of phage display libraries using human antibody framework families. Deep sequencing analysis revealed that all libraries displayed different CDRH3 repertoires, but the one derived from lymph nodes of naïve mice was the most diverse. Library performance was assessed by in vitro selection. For both organs, immunization increased substantially the frequency of molecules able to bind to the immunogen. The library derived from lymph nodes from naïve mice, however, was the most effective in generating diverse and high affinity candidates. These results illustrate that the use of a biased CDRH3 repertoire increases the performance of libraries, but reduces the clonal diversity, which may be detrimental for certain strategies.

  17. Computed tomography in the diagnosis of steroidal hepatopathy in a dog: case report

    Directory of Open Access Journals (Sweden)

    D.C Oliveira

    2011-02-01

    Full Text Available It is reported a case of an eight-year-old Yorkshire Terrier dog, with a history of prolonged use of prednisone in a dosage of 1mg/kg of body weight each 24 hours during two years. The helical computed tomography revealed hepatomegaly associated to a hyperattenuation of the parenchyma, with a radiodensity value of 82.55 Hounsfield units (HU. The spleen presented a mean radiodensity of 57.17HU, and a radiodensity difference of 25.38HU was observed between the two organs. Based on the history and findings of imaging technique, it was determined the presumptive diagnosis of steroidal hepatopathy compatible with accumulation of hepatic glycogen. It was concluded that computed tomography enabled the characterization of hepatic injury and the presumed diagnosis of steroidal hepatopathy

  18. Computed tomography in the diagnosis of steroidal hepatopathy in a dog: case report

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, D.C; Costa, L.A.V.S.; Lopes, B.F.; Lanis, A.B.; Borlini, D.C.; Costa, F.S., E-mail: danielcapucho@gmail.co [Universidade Federal do Espirito Santo (UFES), Vitroria, ES (Brazil). Dept. de Medicina Veterinaria; Maia Junior, J.A. [Centro de Escolas de Formacao de Tecnicos em Radiologia, Vila Velha, ES (Brazil)

    2011-02-15

    It is reported a case of an eight-year-old Yorkshire Terrier dog, with a history of prolonged use of prednisone in a dosage of 1mg/kg of body weight each 24 hours during two years. The helical computed tomography revealed hepatomegaly associated to a hyper attenuation of the parenchyma, with a radiodensity value of 82.55 Hounsfield units (HU). The spleen presented a mean radiodensity of 57.17HU, and a radiodensity difference of 25.38HU was observed between the two organs. Based on the history and findings of imaging technique, it was determined the presumptive diagnosis of steroidal hepatopathy compatible with accumulation of hepatic glycogen. It was concluded that computed tomography enabled the characterization of hepatic injury and the presumed diagnosis of steroidal hepatopathy. (author)

  19. The morphological changes in lymphoid organs and peripheral blood indicators in rats after peroral administration of gold nanoparticles

    Science.gov (United States)

    Bucharskaya, A. B.; Pakhomy, S. S.; Zlobina, O. V.; Maslyakova, G. N.; Matveeva, O. V.; Bugaeva, I. O.; Navolokin, N. A.; Khlebtsov, B. N.; Bogatyrev, V. A.; Khlebtsov, N. G.; Tuchin, V. V.

    2016-03-01

    The wide application of nanotechnologies in medicine requires the careful study of various aspects of their potential safety. The effects of prolonged peroral administration of gold nanoparticles on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory animals were investigated in experiment. The gold nanospheres functionalized with thiolated polyethylene glycol sizes 2, 15 and 50 nm were administered orally for 15 days to outbred white rats at a dosage of 190 μg/kg of animal body weight. The standard histological and hematological staining were used for morphological study of lymphoid organs and bone marrow smears. The size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood, especially pronounced after administration of gold nanoparticles with size of 50 nm. The stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone marrow. The signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes, which were showed as the increasing number of immunoblasts and large lymphocytes. The quantitative changes of cellular component morphology of lymphoid organs due to activation of migration, proliferation and differentiation of immune cells indicate the presence of immunostimulation effect of gold nanoparticles.

  20. A study of lymphoid organs and serum proinflammatory cytokines in pigs infected with African swine fever virus genotype II.

    Science.gov (United States)

    Zakaryan, Hovakim; Cholakyans, Victorya; Simonyan, Lusine; Misakyan, Alla; Karalova, Elena; Chavushyan, Andranik; Karalyan, Zaven

    2015-06-01

    African swine fever virus (ASFV), the causative agent of one of the most important viral diseases of domestic pigs for which no vaccine is available, causes immune system disorders in infected animals. In this study, the serum levels of proinflammatory cytokines, as well as the histological and cellular constitution of lymphoid organs of pigs infected with ASFV genotype II were investigated. The results showed a high degree of lymphocyte depletion in the lymphoid organs, particularly in the spleen and lymph nodes, where ASFV infection led to a twofold decrease in the number of lymphocytes on the final day of infection. Additionally, ASFV-infected pigs had atypical forms of lymphocytes found in all lymphoid organs. In contrast to lymphocytes, the number of immature immune cells, particularly myelocytes, increased dramatically and reached a maximum on day 7 postinfection. The serum levels of TNF-α, IL-1β, IL-6, and IL-8 were evaluated. Proinflammatory cytokines showed increased levels after ASFV infection, with peak values at 7 days postinfection, and this highlights their role in the pathogenesis of ASFV. In conclusion, this study showed that ASFV genotype II, like other highly virulent strains, causes severe pathological changes in the immune system of pigs.

  1. Lymphoid organ cell culture system from Penaeus monodon (Fabricius) as a platform for white spot syndrome virus and shrimp immune-related gene expression.

    Science.gov (United States)

    Jose, S; Jayesh, P; Sudheer, N S; Poulose, G; Mohandas, A; Philip, R; Singh, I S Bright

    2012-05-01

    Shrimp cell lines are yet to be reported and this restricts the prospects of investigating the associated viral pathogens, especially white spot syndrome virus (WSSV). In this context, development of primary cell cultures from lymphoid organs was standardized. Poly-l-lysine-coated culture vessels enhanced growth of lymphoid cells, while the application of vertebrate growth factors did not, except insulin-like growth factor-1 (IGF-1). Susceptibility of the lymphoid cells to WSSV was confirmed by immunofluoresence assay using monoclonal antibody against the 28 kDa envelope protein of WSSV. Expression of viral and immune-related genes in WSSV-infected lymphoid cultures could be demonstrated by RT-PCR. This emphasizes the utility of lymphoid primary cell culture as a platform for research in virus-cell interaction, virus morphogenesis, up and downregulation of shrimp immune-related genes, and also for the discovery of novel drugs to combat WSSV in shrimp culture.

  2. Secondary Lymphoid Organ Homing Phenotype of Human Myeloid Dendritic Cells Disrupted by an Intracellular Oral Pathogen

    Science.gov (United States)

    Miles, Brodie; Zakhary, Ibrahim; El-Awady, Ahmed; Scisci, Elizabeth; Carrion, Julio; O'Neill, John C.; Rawlings, Aaron; Stern, J. Kobi; Susin, Cristiano

    2014-01-01

    Several intracellular pathogens, including a key etiological agent of chronic periodontitis, Porphyromonas gingivalis, infect blood myeloid dendritic cells (mDCs). This infection results in pathogen dissemination to distant inflammatory sites (i.e., pathogen trafficking). The alteration in chemokine-chemokine receptor expression that contributes to this pathogen trafficking function, particularly toward sites of neovascularization in humans, is unclear. To investigate this, we utilized human monocyte-derived DCs (MoDCs) and primary endothelial cells in vitro, combined with ex vivo-isolated blood mDCs and serum from chronic periodontitis subjects and healthy controls. Our results, using conditional fimbria mutants of P. gingivalis, show that P. gingivalis infection of MoDCs induces an angiogenic migratory profile. This profile is enhanced by expression of DC-SIGN on MoDCs and minor mfa-1 fimbriae on P. gingivalis and is evidenced by robust upregulation of CXCR4, but not secondary lymphoid organ (SLO)-homing CCR7. This disruption of SLO-homing capacity in response to respective chemokines closely matches surface expression of CXCR4 and CCR7 and is consistent with directed MoDC migration through an endothelial monolayer. Ex vivo-isolated mDCs from the blood of chronic periodontitis subjects, but not healthy controls, expressed a similar migratory profile; moreover, sera from chronic periodontitis subjects expressed elevated levels of CXCL12. Overall, we conclude that P. gingivalis actively “commandeers” DCs by reprogramming the chemokine receptor profile, thus disrupting SLO homing, while driving migration toward inflammatory vascular sites. PMID:24126519

  3. Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Matthias S Matter

    Full Text Available Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destruction of liver cells by the host's own immune response. Similarly, after infection with lymphocytic choriomeningitis virus (LCMV in mice, the adaptive immune response causes liver cell damage, choriomeningitis and destruction of lymphoid organ architecture. The immunopathological sequel during LCMV infection has been attributed to cytotoxic CD8(+ T cells. However, we now show that during LCMV infection CD4(+ T cells selectively induced the destruction of splenic marginal zone and caused liver cell damage with elevated serum alanin-transferase (ALT levels. The destruction of the splenic marginal zone by CD4(+ T cells included the reduction of marginal zone B cells, marginal zone macrophages and marginal zone metallophilic macrophages. Functionally, this resulted in an impaired production of neutralizing antibodies against LCMV. Furthermore, CD4(+ T cells reduced B cells with an IgM(highIgD(low phenotype (transitional stage 1 and 2, marginal zone B cells, whereas other B cell subtypes such as follicular type 1 and 2 and germinal center/memory B cells were not affected. Adoptive transfer of CD4(+ T cells lacking different important effector cytokines and cytolytic pathways such as IFNγ, TNFα, perforin and Fas-FasL interaction did reveal that these cytolytic pathways are redundant in the induction of immunopathological sequel in spleen. In conclusion, our results define an important role of CD4(+ T cells in the induction of immunopathology in liver and spleen. This includes the CD4(+ T cell mediated destruction of the splenic marginal zone with consecutively impaired protective neutralizing antibody responses.

  4. Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm.

    Science.gov (United States)

    Spear, Rafaelle; Boytard, Ludovic; Blervaque, Renaud; Chwastyniak, Maggy; Hot, David; Vanhoutte, Jonathan; Staels, Bart; Lemoine, Yves; Lamblin, Nicolas; Pruvot, François-René; Haulon, Stephan; Amouyel, Philippe; Pinet, Florence

    2015-05-18

    Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.

  5. Pairing experimentation and computational modelling to understand the role of tissue inducer cells in the development of lymphoid organs

    Directory of Open Access Journals (Sweden)

    Kieran eAlden

    2012-07-01

    Full Text Available The use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insights into the role of tissue inducer cells and associated signalling pathways in the formation and function of lymphoid organs. Despite advances in experimental technologies, the molecular and cellular process orchestrating the formation of a complex 3-dimensional tissue is difficult to dissect using current approaches. Therefore, a robust set of simulation tools have been developed to model the processes involved in lymphoid tissue development. Specifically the role of different tissue inducer cell populations in the dynamic formation of Peyer's Patches has been examined. Utilising approaches from critical systems engineering an unbiased model of lymphoid tissue inducer cell function has been developed, that permits the development of emerging behaviours that are statistically not different from that observed in vivo. These results provide the confidence to utilise statistical methods to explore how the simulator predicts cellular behaviour and outcomes under different physiological conditions. Such methods, known as sensitivity analysis techniques, can provide insight into when a component part of the system (such as a particular cell type, adhesion molecule, or chemokine begins to have an influence on observed behaviour, and quantifies the effect a component part has on the end result: the formation of lymphoid tissue. Through use of such a principled approach in the design, calibration, and analysis of a computer simulation, a robust in silico tool can be developed which can both further the understanding of a biological system being explored, and act as a tool for the generation of hypotheses which can be tested utilising experimental approaches.

  6. Functional contributions of N- and O-glycans to L-selectin ligands in murine and human lymphoid organs.

    Science.gov (United States)

    Arata-Kawai, Hanayo; Singer, Mark S; Bistrup, Annette; Zante, Annemieke van; Wang, Yang-Qing; Ito, Yuki; Bao, Xingfeng; Hemmerich, Stefan; Fukuda, Minoru; Rosen, Steven D

    2011-01-01

    L-selectin initiates lymphocyte interactions with high endothelial venules (HEVs) of lymphoid organs through binding to ligands with specific glycosylation modifications. 6-Sulfo sLe(x), a sulfated carbohydrate determinant for L-selectin, is carried on core 2 and extended core 1 O-glycans of HEV-expressed glycoproteins. The MECA-79 monoclonal antibody recognizes sulfated extended core 1 O-glycans and partially blocks lymphocyte-HEV interactions in lymphoid organs. Recent evidence has identified the contribution of 6-sulfo sLe(x) carried on N-glycans to lymphocyte homing in mice. Here, we characterize CL40, a novel IgG monoclonal antibody. CL40 equaled or surpassed MECA-79 as a histochemical staining reagent for HEVs and HEV-like vessels in mouse and human. Using synthetic carbohydrates, we found that CL40 bound to 6-sulfo sLe(x) structures, on both core 2 and extended core 1 structures, with an absolute dependency on 6-O-sulfation. Using transfected CHO cells and gene-targeted mice, we observed that CL40 bound its epitope on both N-glycans and O-glycans. Consistent with its broader glycan-binding, CL40 was superior to MECA-79 in blocking lymphocyte-HEV interactions in both wild-type mice and mice deficient in forming O-glycans. This superiority was more marked in human, as CL40 completely blocked lymphocyte binding to tonsillar HEVs, whereas MECA-79 inhibited only 60%. These findings extend the evidence for the importance of N-glycans in lymphocyte homing in mouse and indicate that this dependency also applies to human lymphoid organs.

  7. Effects of lactational exposure of olanzapine and risperidone on hematology and lymphoid organs histopathology: a comparative study in mice neonates.

    Science.gov (United States)

    Mishra, Akash C; Mohanty, Banalata

    2010-05-25

    Body weight gain, sexual/reproductive dysfunction and hematological abnormalities are serious consequences of atypical antipsychotics treatment. No attempts however have been made preclinically to elucidate the adverse hematological impacts. Presently, effects of lactational exposure of olanzapine (4, 8 and 10 mg/kg) and risperidone (1 and 2 mg/kg) on hematology as well as lymphoid organ histopathology of mice neonates were investigated. Both olanzapine and risperidone transfers through milk and make the neonates susceptible to their adverse side effects. Corticosterone elevation tendency of both the drugs further enhance the susceptibility for immune dysfunction. Analysis of total and differential leukocytes counts revealed neutropenia with all the doses of olanzapine but only with risperidone 2mg/kg. Weight analysis and histopathology of thymus and spleen indicated a state of suppression; less in the risperidone-exposed groups. Significant plasma corticosterone elevation occurred on 4 and 8 mg/kg olanzapine exposures but not with 10 mg/kg as well as with both the risperidone doses. Elevation of plasma prolactin levels occurred dose-dependently for both the drugs. Hematological toxicity (neutropenia) might be the direct toxic effects of the drugs/unstable metabolites on circulating neutrophils and/or on the bone marrow hemopoietic cells. Direct toxicity of the drugs might also have suppressed the lymphoid organs thymus and spleen. Further, it could be associated to hormonal imbalance induced by adverse pharmacological effects of the drugs on the endocrine system. Suppression of lymphoid organs in olanzapine groups might have resulted because of corticosteronemia and hyperprolactinemia, while in risperidone it could be mediated by pronounced hyperprolactinemic effect alone.

  8. Probiotic feeding affects T cell populations in blood and lymphoid organs in chickens.

    Science.gov (United States)

    Asgari, F; Madjd, Z; Falak, R; Bahar, M A; Nasrabadi, M Heydari; Raiani, M; Shekarabi, M

    2016-11-30

    This study was performed to evaluate the effects of Lactobacillus acidophilus bacteria as a probiotic on chicken T cell subset populations in peripheral blood and lymphoid tissues. Thirty chickens were divided into three groups and fed sterilised cow milk, a mixture of milk and L. acidophilus (probiotic), or neither, as the control group. Chickens were euthanised after 14 and 21 days, and whole blood and ileal, bursal, and caecal tonsillar tissues were collected. The populations of T cell subsets, including CD4(+), CD8(+), and TCR1(+) cells, were evaluated by immunohistochemistry and flow cytometry. After 21 days of treatment the percentage of blood CD4(+), CD8(+), and TCR1(+) cells was significantly higher in the probiotic-fed group than in the control group. After 14 days of treatment, a significantly greater number of CD4(+) T cells were found in the ileum of probiotic-fed chickens than in chickens from the other two groups. This difference was even greater after 21 days. In addition, after 21 days, a significantly greater number of TCR1(+) cells were found in the caecal tonsils of milk-fed chickens than in chickens from the control group. The findings indicate that probiotics may alter the distribution of T cells in the blood and lymphoid tissues in young chickens; however, transient changes in lymphoid tissues indicate that probiotics likely do not permanently affect mucosal immunity.

  9. Glycogenic hepatopathy in young adults: a case series

    Directory of Open Access Journals (Sweden)

    Marco Silva

    Full Text Available Glycogenic hepatopathy is a rare and underecognized complication in long-standing poorly controlled type 1 diabetes mellitus patients. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics, such as nonalcoholic fatty liver disease. Glycogenic hepatopathy is characterized by the combination of poorly controlled diabetes, acute liver injury with marked elevation in serum aminotransferases, and the characteristic histological features on liver biopsy. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control. In this report, we describe four cases of adult patients presenting elevated serum transaminases and hepatomegaly with a history of poorly controlled type I diabetes mellitus. One of the patients had also elevated amylase and lipase in the serum, without clinical or imagiologic evidence of acute pancreatitis. Liver biopsy was performed in all patients and revealed glycogenic hepatopathy. Clinician's awareness of glycogenic hepatopathy should prevent diagnostic delay or misdiagnosis and will provide better insight and management for this condition.

  10. Total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-05-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen.

  11. Gel-Trapped Lymphorganogenic Chemokines Trigger Artificial Tertiary Lymphoid Organs and Mount Adaptive Immune Responses In Vivo.

    Science.gov (United States)

    Kobayashi, Yuka; Watanabe, Takeshi

    2016-01-01

    We previously generated artificial lymph node-like tertiary lymphoid organs (artTLOs) in mice using lymphotoxin α-expressing stromal cells. Here, we show the construction of transplantable and functional artTLOs by applying soluble factors trapped in slow-releasing gels in the absence of lymphoid tissue organizer stromal cells. The resultant artTLOs were easily removable, transplantable, and were capable of attracting memory B and T cells. Importantly, artTLOs induced a powerful antigen-specific secondary immune response, which was particularly pronounced in immune-compromised hosts. Synthesis of functionally stable immune tissues/organs like those described here may be a first step to eventually develop immune system-based therapeutics. Although much needs to be learned from the precise mechanisms of action, they may offer ways in the future to reestablish immune functions to overcome hitherto untreatable diseases, including severe infection, cancer, autoimmune diseases, and various forms of immune deficiencies, including immune-senescence during aging.

  12. Protein deficiency alters impact of intestinal nematode infection on intestinal, visceral and lymphoid organ histopathology in lactating mice.

    Science.gov (United States)

    Starr, Lisa M; Odiere, Maurice R; Koski, Kristine G; Scott, Marilyn E

    2014-05-01

    Protein deficiency impairs local and systemic immune responses to Heligmosomoides bakeri infection but little is known about their individual and interactive impacts on tissue architecture of maternal lymphoid (thymus, spleen) and visceral (small intestine, kidney, liver, pancreas) organs during the demanding period of lactation. Using a 2 × 2 factorial design, pregnant CD1 mice were fed a 24% protein sufficient (PS) or a 6% protein deficient (PD) isoenergetic diet beginning on day 14 of pregnancy and were infected with 100 H. bakeri larvae four times or exposed to four sham infections. On day 20 of lactation, maternal organs were examined histologically and serum analytes were assayed as indicators of organ function. The absence of villus atrophy in response to infection was associated with increased crypt depth and infiltration of mast cells and eosinophils but only in lactating dams fed adequate protein. Infection-induced lobular liver inflammation was reduced in PD dams, however, abnormalities in the kidney caused by protein deficiency were absent in infected dams. Bilirubin and creatinine were highest in PD infected mice. Infection-induced splenomegaly was not due to an increase in the lymphoid compartment of the spleen. During lactation, infection and protein deficiency have interactive effects on extra-intestinal pathologies.

  13. Alterations of morphology of lymphoid organs and peripheral blood indicators under the influence of gold nanoparticles in rats

    Directory of Open Access Journals (Sweden)

    Alla B. Bucharskaya

    2016-01-01

    Full Text Available At present, gold nanoparticles (GNPs are widely used in biomedical applications such as cancer diagnostics and therapy. Accordingly, the potential toxicity hazards of these nanomaterials and human safety concerns are gaining significant attention. Here, we report the effects of prolonged peroral administration of GNPs with different sizes (2, 15 and 50nm on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory animals. The experiment was conducted on 24 white mongrel male rats weighing 180–220g, gold nanospheres sizes 2, 15 and 50nm were administered orally for 15 days at a dosage of 190μg/kg of animal body weight. The GNPs were conjugated with polyethylene glycol to increase their biocompatibility and bioavailability. The size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood, especially pronounced after administration of GNPs with size of 50nm. The stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone marrow. The signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes, which were showed as the increasing number of immunoblasts and large lymphocytes. The quantitative changes of cellular component morphology of lymphoid organs due to activation of migration, proliferation and differentiation of immune cells indicate the presence of immunostimulation effect of GNPs.

  14. Neuropilin-1 expression characterizes T follicular helper (Tfh) cells activated during B cell differentiation in human secondary lymphoid organs.

    Science.gov (United States)

    Renand, Amédée; Milpied, Pierre; Rossignol, Julien; Bruneau, Julie; Lemonnier, François; Dussiot, Michael; Coulon, Séverine; Hermine, Olivier

    2013-01-01

    T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. Tfh cells regulate the differentiation and survival of activated B cells outside and inside germinal centers (GC) of secondary lymphoid organs. They act through cognate contacts with antigen-presenting B cells, but there is no current marker to specifically identify those Tfh cells which productively interact with B cells. Here we show that neuropilin 1 (Nrp1), a cell surface receptor, is selectively expressed by a subset of Tfh cells in human secondary lymphoid organs. Nrp1 expression on Tfh cells correlates with B cell differentiation in vivo and in vitro, is transient, and can be induced upon co-culture with autologous memory B cells in a cell contact-dependent manner. Comparative analysis of ex vivo Nrp1(+) and Nrp1(-) Tfh cells reveals gene expression modulation during activation. Finally, Nrp1 is expressed by malignant Tfh-like cells in a severe case of angioimmunoblastic T-cell lymphoma (AITL) associated with elevated terminal B cell differentiation. Thus, Nrp1 is a specific marker of Tfh cells cognate activation in humans, which may prove useful as a prognostic factor and a therapeutic target in neoplastic diseases associated with Tfh cells activity.

  15. Prion pathogenesis and secondary lymphoid organs (SLO): tracking the SLO spread of prions to the brain.

    Science.gov (United States)

    Mabbott, Neil A

    2012-01-01

    Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrP (Sc), an abnormally folded isoform of the cellular prion protein (PrP (C)), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases.

  16. Quantitative studies of lymphoid organs, blood and lymph in inbred athymic and euthymic LEW rats under germfree and specified-pathogen-free conditions

    DEFF Research Database (Denmark)

    Klausen, B; Hougen, H P

    1987-01-01

    Four groups of inbred male LEW rats were examined: A, germfree athymic; B, specified pathogen free (SPF) athymic; C, germfree euthymic; D, SPF euthymic. All animals were killed at 18 weeks and compared with respect to body weight, histological appearance and cell density of the lymphoid organs......, haematological values and differential counts of bone marrow, peripheral blood and lymph. Athymic rats had a lower body weight, less densely populated lymphoid organs, and fewer lymphocytes in the blood and lymph compared with euthymic animals. No difference was seen between athymic rats under germfree and SPF...

  17. Glucocorticoid-induced laminitis with hepatopathy in a Thoroughbred filly.

    Science.gov (United States)

    Ryu, Seung Ho; Kim, Byung Sun; Lee, Chang Woo; Yoon, Junghee; Lee, Yonghoon Lyon

    2004-09-01

    A 3-year-old Thoroughbred filly was referred to the Equine Hospital, Korea Racing Association for evaluation of hematuria, inappetite, weight loss and depression. From 25 days prior to admission, the horse was treated for right carpal lameness with 20 mg intramuscular administration of triamcinolone acetonide per day for consecutive 10 days by a local veterinarian. Clinical and laboratory findings included vaginal hyperemia, flare in bladder wall, neutrophilia, lymphopenia, polyuria, polydipsia and laminitis in the end. High activities of aspartate transaminase and gamma glutamyltransferase and high concentration of total bilirubin indicated hepatopathy. Further hematology, serum biochemistry and urinalysis did not reveal any abnormalities. Medical history, physical and clinicopathologic findings suggest that the laminitis and hepatopathy in this horse were most likely induced by repeated administration of exogenous corticosteroid. However, guarded prognosis of treating laminitis undermined the benefit of improvement of hematuria following electroacupuncture stimulation. The combined stimulation of kidney related acupoints (Shen Peng, Shen Shu), lumber related acupoints (Yao Qian, Yao Zhong) and associate acupoints (Guan Yuan Shu, Bai Hui) at 5Hz, 1-2V, for 40 minutes was of value in the treatment of hematuria. This case shows that horses under steroids may exhibit laminitis and steroid hepatopathy. Early recognition and good management of laminitis are important in the limitation of complications.

  18. Context dependent development of lymphoid organ mesenchymal subsets fromBP3-Gp38+ PDGFRβ++CD34+ vascular adventitial precursors

    DEFF Research Database (Denmark)

    Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger;

    Lymphoid associated mesenchymal stromal cells are believed to play essential roles in immune and organ homeostasis however our knowledge regarding the functional heterogenity and ontogeny of these cells remains limited.......Lymphoid associated mesenchymal stromal cells are believed to play essential roles in immune and organ homeostasis however our knowledge regarding the functional heterogenity and ontogeny of these cells remains limited....

  19. Virus replication cycle of white spot syndrome virus in secondary cell cultures from the lymphoid organ of Litopenaeus vannamei.

    Science.gov (United States)

    Li, Wenfeng; Desmarets, Lowiese M B; De Gryse, Gaëtan M A; Theuns, Sebastiaan; Van Tuan, Vo; Van Thuong, Khuong; Bossier, Peter; Nauwynck, Hans J

    2015-09-01

    The replication cycle of white spot syndrome virus (WSSV) was investigated in secondary cell cultures from the lymphoid organ of Litopenaeus vannamei. The secondary cells formed a confluent monolayer at 24 h post-reseeding, and this monolayer could be maintained for 10 days with a viability of 90 %. Binding of WSSV to cells reached a maximum (73 ± 3 % of cells and 4.84 ± 0.2 virus particles per virus-binding cell) at 120 min at 4 °C. WSSV entered cells by endocytosis. The co-localization of WSSV and early endosomes was observed starting from 30 min post-inoculation (p.i.). Double indirect immunofluorescence staining showed that all cell-bound WSSV particles entered these cells in the period between 0 and 60 min p.i. and that the uncoating of WSSV occurred in the same period. After 1 h inoculation at 27 °C, the WSSV nucleocapsid protein VP664 and envelope protein VP28 started to be synthesized in the cytoplasm from 1 and 3 h p.i., and were transported into nuclei from 3 and 6 h p.i., respectively. The percentage of cells that were VP664- and VP28-positive in their nuclei peaked (50 ± 4 %) at 12 h p.i. Quantitative PCR showed that WSSV DNA started to be synthesized from 6 h p.i. In vivo titration of the supernatants showed that the progeny WSSV were released from 12 h p.i. and peaked at 18 h p.i. In conclusion, the secondary cell cultures from the lymphoid organ were proven to be ideal for examination of the replication cycle of WSSV.

  20. Atrophy of the lymphoid organs and suppression of antibody response caused by velogenic Newcastle disease virus infection in chickens.

    Science.gov (United States)

    Ezema, Wilfred Sunday; Eze, Didacus Chukwuemeka; Shoyinka, Shodeinde Vincent Olu; Okoye, John Osita Arinze

    2016-12-01

    This project was undertaken to study the immunosuppressive capabilities of velogenic viscerotropic pathotype of Newcastle disease virus (VVNDV) infection in cockerels. Two hundred six-week-old cockerels were divided into four groups. Groups B/VUC and C/VC were vaccinated with LaSota in drinking water at 6 weeks of age. Groups C/VC and D/UC were challenged with VVNDV at 8 weeks of age. Three days post challenge (PC), the cockerels in group D/UC came down with clinical signs which included depression and greenish diarrhoea. Total mortality was 74.6 %. The C/VC cockerels showed no clinical signs. But both challenged groups showed significant weight loss, significant loss of total serum proteins, globulin and albumen (P < 0.05). These losses were more severe in the D/UC than in the C/VC. There was severe atrophy of the bursa, spleen and thymus in both groups. Histopathology showed severe necrosis and depletion of the lymphocytes in the three lymphoid organs. However, the lesions were more severe in the D/UC than in C/VC cockerels. On day 28, PC groups B/VUC, C/VIC and D/UIC were revaccinated with LaSota. The haemagglutination inhibition antibody response on days 35, 42 and 49 PC was very low in groups C/VIC and D/UIC when compared with B/VUC cockerels. These observations show that VVNDV infection both clinical and subclinical can cause immunosuppression and vaccine failure due to severe destruction of the lymphocytes in the lymphoid organs. This will be a serious problem for poultry production in those countries where the disease is enzootic.

  1. IL-27 in human secondary lymphoid organs attracts myeloid dendritic cells and impairs HLA class I-restricted antigen presentation.

    Science.gov (United States)

    Morandi, Fabio; Di Carlo, Emma; Ferrone, Soldano; Petretto, Andrea; Pistoia, Vito; Airoldi, Irma

    2014-03-15

    Different cytokines play crucial roles in inflammation and in polarizing immune responses, including IL-27 that exerts pro- and anti-inflammatory functions. Although the activity of IL-27 is well characterized in murine immune cells, only limited information is available regarding the natural cellular sources of IL-27 in humans and its effects on human immune cells. Dendritic cells (DCs) are the most potent professional APCs that in the immature state are positioned throughout peripheral tissues by acting as sentinels, sensing the presence of Ags. Activated DCs migrate into the lymph nodes and direct Ag-specific T cell responses, thus acting as key players in both adaptive and innate immunity. In this study we asked whether IL-27 is produced by human secondary lymphoid organs and what is its functional role on human DCs. To our knowledge, we provide the first evidence that 1) in lymph nodes, macrophages are the major source for IL-27; 2) immature and mature human DCs express functional IL-27R; 3) IL-27 exerts immunosuppressive activity by crippling the Ag processing machinery in immature DCs under steady-state conditions and after pulsing with a viral Ag; and 4) IL-27 is chemotactic for human DCs. Our findings highlight novel mechanisms underlying the immunosuppressive activity of IL-27, suggesting that this cytokine may function as a homeostatic cytokine in secondary lymphoid organs by limiting duration and/or intensity of ongoing adaptive immune responses. The results presented in this study pave the way to future studies aimed at investigating whether dysregulation of IL-27 expression and function may be involved in pathogenesis of autoimmune disease and cancer.

  2. Identification of stable reference genes for quantitative PCR in cells derived from chicken lymphoid organs.

    Science.gov (United States)

    Borowska, D; Rothwell, L; Bailey, R A; Watson, K; Kaiser, P

    2016-02-01

    Quantitative polymerase chain reaction (qPCR) is a powerful technique for quantification of gene expression, especially genes involved in immune responses. Although qPCR is a very efficient and sensitive tool, variations in the enzymatic efficiency, quality of RNA and the presence of inhibitors can lead to errors. Therefore, qPCR needs to be normalised to obtain reliable results and allow comparison. The most common approach is to use reference genes as internal controls in qPCR analyses. In this study, expression of seven genes, including β-actin (ACTB), β-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-glucuronidase (GUSB), TATA box binding protein (TBP), α-tubulin (TUBAT) and 28S ribosomal RNA (r28S), was determined in cells isolated from chicken lymphoid tissues and stimulated with three different mitogens. The stability of the genes was measured using geNorm, NormFinder and BestKeeper software. The results from both geNorm and NormFinder were that the three most stably expressed genes in this panel were TBP, GAPDH and r28S. BestKeeper did not generate clear answers because of the highly heterogeneous sample set. Based on these data we will include TBP in future qPCR normalisation. The study shows the importance of appropriate reference gene normalisation in other tissues before qPCR analysis.

  3. Age-associated alterations in sympathetic noradrenergic innervation of primary and secondary lymphoid organs in female Fischer 344 rats.

    Science.gov (United States)

    ThyagaRajan, Srinivasan; Madden, Kelley S; Teruya, Brian; Stevens, Suzanne Y; Felten, David L; Bellinger, Denise L

    2011-04-01

    Normal aging processes, as well as, psychological stress affect the immune system; each can act alone, or interact with each other, to cause dysregulation of immune function substantially altering physical and mental health. The sympathetic nervous system (SNS), a major mediator of stress effects on immune function, is significantly affected by normal aging process, and stress can affect aging of the SNS. Previously, we have shown age-associated changes in sympathetic noradrenergic (NA) innervation of lymphoid organs in male rodents that affect immune regulation. The purpose of this study was to investigate sympathetic innervation of lymphoid organs and associated alterations in immune responses in young and aging female Fischer 344 (F344) rats. Histofluorescence and immunocytochemistry for NA innervation, and neurochemistry for norepinephrine (NE) levels were performed in the thymus, spleen, and mesenteric lymph nodes (MLN) isolated from 3-month-old young (normal estrous cycle), 8- to 9-month-old (onset of irregular estrous cycling), and 24-25 month, and 30-31 month female F344 rats (acyclic) at diestrus based on vaginal smears. Age-related alterations in natural killer (NK) cell activity, interleukin-2 (IL-2) and interferon-γ (IFN-γ) production, T and B lymphocyte proliferation were examined in splenocytes. Sympathetic NA innervation and NE levels increased with aging in the thymus, declined in spleen and MLN, and was accompanied by significant reductions in NK cell activity, IL-2 and IFN-γ production, and T and B cell proliferation in old female rats. In 8-9 mo rats, NE levels in the hilar region of the spleen and IFN-γ production were unaltered, while NE levels in the end region of the spleen and IL-2 production were reduced. Collectively, these results suggest that aging is characterized by significant alterations in sympathetic NA innervation in the thymus, spleen, and MLN associated with immunosuppression, and that there is a marked shift in NA activity

  4. TLR activation excludes circulating naive CD8+ T cells from gut-associated lymphoid organs in mice.

    Science.gov (United States)

    Heidegger, Simon; Kirchner, Sophie-Kathrin; Stephan, Nicolas; Bohn, Bernadette; Suhartha, Nina; Hotz, Christian; Anz, David; Sandholzer, Nadja; Stecher, Bärbel; Rüssmann, Holger; Endres, Stefan; Bourquin, Carole

    2013-05-15

    The trafficking of effector T cells is tightly regulated by the expression of site-specific sets of homing molecules. In contrast, naive T cells are generally assumed to express a uniform pattern of homing molecules and to follow a random distribution within the blood and secondary lymphoid organs. In this study, we demonstrate that systemic infection fundamentally modifies the trafficking of circulating naive CD8(+) T cells. We show that on naive CD8(+) T cells, the constitutive expression of the integrin α4β7 that effects their entry into GALT is downregulated following infection of mice with Salmonella typhimurium. We further show that this downregulation is dependent on TLR signaling, and that the TLR-activated naive CD8(+) T cells are blocked from entering GALT. This contrasts strongly with Ag-experienced effector T cells, for which TLR costimulation in the GALT potently upregulates α4β7 and enhances trafficking to intestinal tissues. Thus, TLR activation leads to opposite effects on migration of naive and effector CD8(+) T cells. Our data identify a mechanism that excludes noncognate CD8(+) T cells from selected immune compartments during TLR-induced systemic inflammation.

  5. Effects of dietary Fusarium mycotoxins on intestinal lymphocyte subset populations, cell proliferation and histological changes in avian lymphoid organs.

    Science.gov (United States)

    Girish, C K; Smith, T K; Boermans, H J; Anil Kumar, P; Girgis, G N

    2010-10-01

    An experiment was conducted to investigate the effects of dietary Fusarium mycotoxins on gut immunity, cell proliferation, and histology of avian lymphoid organs. The efficacy of a polymeric glucomannan mycotoxin adsorbent (GMA) was also determined. Seventy-two one-day-old male turkey poults were fed corn, wheat, and soybean meal-based diets for 21 days. Diets included control grains, contaminated grains and contaminated grains +0.2% GMA. The major contaminant was deoxynivalenol (3.9 μg/g) with lesser amounts of zearalenone (0.67-0.75 μg/g), 15-acetyl-deoxynivalenol (0.34 μg/g) and HT-2 toxin (0.078-0.085 μg/g). T- and B-lymphocyte populations and crypt cellular proliferation in duodenum, jejunum, ileum and cecal tonsil were measured immunohistochemically on day 14 and 21. Histological changes were recorded after 14 and 21 days of feeding. Feeding contaminated grains significantly increased the percentage of B-lymphocytes in ileum on day 14, and reduced (Pcontaminated diets also caused a reduction (Pcontaminated with Fusarium mycotoxins results in adverse effects on gut immunity and mucosal cell proliferation.

  6. Distribution of lymphoid neoplasms in China: analysis of 4,638 cases according to the World Health Organization classification.

    Science.gov (United States)

    Sun, Jian; Yang, Qunpei; Lu, Zhaohui; He, Miaoxia; Gao, Li; Zhu, Minghua; Sun, Lu; Wei, Lixin; Li, Min; Liu, Cuiling; Zheng, Jie; Liu, Weiping; Li, Gandi; Chen, Jie

    2012-09-01

    To estimate the distribution of lymphoid neoplasms in China, we conducted a comprehensive analysis, based on subtype, age, sex, and lesion, of primary and resected biopsy specimens of 4,638 lymphoid neoplasms diagnosed from 2004 to 2008 at 5 large hospitals. Of the 4,638 patients, mature B-cell neoplasms accounted for 64.3% of all lymphoid neoplasms, mature T/NK-cell neoplasms for 23.3%, and Hodgkin lymphoma for 8.6%. The most common subtype was diffuse large B-cell lymphoma (36.2%), followed by extranodal NK/T-cell lymphoma, nasal type (11.0%), classic Hodgkin lymphoma (8.4%), extranodal marginal zone B-cell lymphoma (7.7%), plasmacytic neoplasm (5.0%), and peripheral T-cell lymphoma, not otherwise specified (3.9%). For most lymphoid neoplasm subtypes, male subjects showed higher rates than female subjects. In summary, our study showed that the epidemiologic features of lymphoid neoplasms in China are distinct from those in Western countries and similar in many ways to those in other countries of the Far East.

  7. Lymph node and lymphoid organs fine needle aspiration cytology: historical background.

    Science.gov (United States)

    Cozzolino, Immacolata; Vigliar, Elena; Vetrani, Antonio; Zeppa, Pio

    2012-01-01

    Lymph node has probably been the first target of Fine Needle Cytology (FNC) and among the latest to be accepted as an affordable diagnostic procedure. In 1912, dr. Hirschfeld performed FNC to diagnose cutaneous lymphomas and other tumours. Subsequently FNC was used to diagnose lymphoblastoma and splenic FNC to diagnose leishmaniasis on Romanowsky-stained smears. One of the first systematic study on lymph node FNC was then performed at John Hopkins Hospital, in Baltimore (USA) using FNC and Romanowsky stain on air-dried smears. In the twenties, two independent groups from Memorial Hospital (New York, USA), worked on FNC of a large scale of different human pathologies. One of this study reported 1,405 diagnoses of cancer and other diseases by means of FNC, mainly performed on lymph nodes (662 cases). In the sixties, at the Karolinska Hospital (Stockholm, Sweden) a group of cytopathologists started a Cytopathology Service available to the whole Institution, which exploited all fields of FNC. Since then, the procedure spread all over the word and nowadays it is routinely used for the diagnosis of different organs and pathologies including lymph node. Distinguished cytopathologists have worked on lymph nodal FNC producing significant advances and highlighting advantages and inevitable limitations of the technique. Despite some persistent criticism, FNC is a generally accepted procedure in the first diagnosis of lymph nodes enlargement. Moreover, numerous studies have demonstrated that vital cells obtained by FNC are excellent samples suitable for molecular evaluation, offering new challenging application to lymph node FNC.

  8. Green Brazilian Propolis Action on Macrophages and Lymphoid Organs of Chronically Stressed Mice

    Directory of Open Access Journals (Sweden)

    Fabiane Missima

    2008-01-01

    Full Text Available Stress is a generic term that summarizes how psychosocial and environmental factors influence physical and mental well-being. The interaction between stress and immunity has been widely investigated, involving the neuroendocrine system and several organs. Assays using natural products in stress models deserve further investigation. Propolis immunomodulatory action has been mentioned and it has been the subject of scientific investigation in our laboratory. The aim of this study was to evaluate if and how propolis activated macrophages in BALB/c mice submitted to immobilization stress, as well as the histopathological analysis of the thymus, bone marrow, spleen and adrenal glands. Stressed mice showed a higher hydrogen peroxide (H2O2 generation by peritoneal macrophages, and propolis treatment potentiated H2O2 generation and inhibited nitric oxide (NO production by these cells. Histopathological analysis showed no alterations in the thymus, bone marrow and adrenal glands, but increased germinal centers in the spleen. Propolis treatment counteracted the alterations found in the spleen of stressed mice. New research is being carried out in order to elucidate propolis immunomodulatory action during stress.

  9. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

    Science.gov (United States)

    Woon, Heng Giap; Braun, Asolina; Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G; Khanna, Rajiv; Elliot, Michael; Bell, Andrew; Hislop, Andrew D; Tangye, Stuart G; Rickinson, Alan B; Gebhardt, Thomas; Britton, Warwick J; Palendira, Umaimainthan

    2016-08-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

  10. HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells.

    Science.gov (United States)

    Stone, Simone Cardozo; Rossetti, Renata Ariza Marques; Bolpetti, Aline; Boccardo, Enrique; Souza, Patricia Savio de Araujo; Lepique, Ana Paula

    2014-10-01

    Tumors are complex structures containing different types of cells and molecules. The importance of the tumor microenvironment in tumor progression, growth, and maintenance is well-established. However, tumor effects are not restricted to the tumor microenvironment. Molecules secreted by, as well as cells that migrate from tumors, may circulate and reach other tissues. This may cause a series of systemic effects, including modulation of immune responses, and in some cases, leukocytosis and metastasis promotion. Leukocytosis has been described as a poor prognostic factor in patients with cervical cancer. The main etiological factor for cervical cancer development is persistent infection with high oncogenic risk HPV. Our laboratory has been exploring the effects of high oncogenic risk, HPV-associated tumors on lymphoid organs of the host. In the present study, we observed an increase in myeloid cell proliferation and alteration in cell signaling in APCs in the spleen of tumor-bearing mice. In parallel, we characterized the cytokines secreted in the inflammatory and tumor cell compartments in the tumor microenvironment and in the spleen of tumor-bearing mice. We show evidence of constitutive activation of the IL-6/STAT3 signaling pathway in the tumor, including TAMs, and in APCs in the spleen. We also observed that IL-10 is a central molecule in the tolerance toward tumor antigens through control of NF-κB activation, costimulatory molecule expression, and T cell proliferation. These systemic effects over myeloid cells are robust and likely an important problem to be addressed when considering strategies to improve anti-tumor T cell responses.

  11. Does disease-irrelevant intrathecal synthesis in multiple sclerosis make sense in the light of tertiary lymphoid organs?

    Directory of Open Access Journals (Sweden)

    Mickael eBonnan

    2014-03-01

    Full Text Available Although partly disease-irrelevant, intrathecal Ig synthesis is a typical feature of multiple sclerosis (MS and is driven by the tertiary lymphoid organs (TLO. A long-known hallmark of this non-specific intrathecal synthesis is the MRZ pattern, an intrathecal synthesis of Ig against measles, rubella and zoster viruses, which could also be involved in a wide range of pathogens. However, this non-specific synthesis is highly problematic since brain TLO should not be able to drive the clonal expansion of lymphocytes against alien antigens that are thought to be absent in MS brain.We propose to explain the paradox of non-specific intrathecal synthesis by discussing the natural properties of TLO. In fact, besides local antigen-driven clonal expansion, circulating plasmablasts and plasma cells (PC are non-specifically recruited from blood and gain access to survival niches in the inflammatory CNS. This mechanism, which has been described in other inflammatory disorders, takes place in the TLO. As a consequence, PCs recruited in brain mirror the individual’s history of immunization and intrathecal synthesis of IgG in MS may target a broad range of common infectious agents, a hypothesis in line with epidemiological data. Moreover, the immunization schedule and its timing may interfere with PC recruitment. If this hypothesis is correct, the reaction against EBV appears paradoxical: although early infection of MS patients is systematic, intrathecal synthesis is far lower than expected, suggesting a crucial interaction between MS onset and timing of EBV infection. A growing body of evidence suggests that the non-specific intrathecal synthesis observed in MS is also common in many chronic CNS inflammatory disorders. Assuming that cortical TLO in MS are associated with typical sub-pial lesions, we have coined the concept of ‘TLO-pathy’ to describe these lesions and take examples of them from non-MS disorders.

  12. Artery Tertiary Lymphoid Organs Control Multilayered Territorialized Atherosclerosis B-Cell Responses in Aged ApoE−/− Mice

    Science.gov (United States)

    Srikakulapu, Prasad; Hu, Desheng; Yin, Changjun; Mohanta, Sarajo K.; Bontha, Sai Vineela; Peng, Li; Beer, Michael; Weber, Christian; McNamara, Coleen A.; Grassia, Gianluca; Maffia, Pasquale; Manz, Rudolf A.

    2016-01-01

    Objective— Explore aorta B-cell immunity in aged apolipoprotein E-deficient (ApoE−/−) mice. Approach and Results— Transcript maps, fluorescence-activated cell sorting, immunofluorescence analyses, cell transfers, and Ig-ELISPOT (enzyme-linked immunospot) assays showed multilayered atherosclerosis B-cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B-cell–related transcriptomes were identified, and transcript atlases revealed highly territorialized B-cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B-cell genes, including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm although intima plaques preferentially expressed molecules involved in non–B effector responses toward B-cell–derived mediators, that is, Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B-cell recruitment. ATLO B-2 B cells included naive, transitional, follicular, germinal center, switched IgG1+, IgA+, and IgE+ memory cells, plasmablasts, and long-lived plasma cells. ATLOs recruited large numbers of B-1 cells whose subtypes were skewed toward interleukin-10+ B-1b cells versus interleukin-10− B-1a cells. ATLO B-1 cells and plasma cells constitutively produced IgM and IgG and a fraction of plasma cells expressed interleukin-10. Moreover, ApoE−/− mice showed increased germinal center B cells in renal lymph nodes, IgM-producing plasma cells in the bone marrow, and higher IgM and anti–MDA-LDL (malondialdehyde-modified low-density lipoprotein) IgG serum titers. Conclusions— ATLOs orchestrate dichotomic, territorialized, and multilayered B-cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging. PMID:27102965

  13. Dumping syndrome, a cause of acquired glycogenic hepatopathy.

    Science.gov (United States)

    Resnick, Jeffrey M; Zador, Ivan; Fish, Daryl L

    2011-01-01

    A 2-year-old boy, having undergone fundoplication for gastroesophageal reflux disease and fed by gastrostomy, presented with recurrent emesis, syncope with hypoglycemia, and persistently elevated serum liver transaminase levels. Liver biopsy revealed hepatocellular glycogenosis by light and electron microscopy. Further evaluation showed no evidence of diabetes mellitus, glycogen storage disease, or corticosteroid use. Since the hyperglycemic-hyperinsulinemic state of dumping syndrome would provide a mechanism for hepatocellular glycogenosis, the biopsy findings prompted consideration of dumping syndrome. Metabolic evaluation confirmed the diagnosis of dumping syndrome, and appropriate dietary management led to sustained resolution of symptomatology and hypertransaminasemia. Dumping syndrome is proposed to be a cause of hepatocellular glycogenosis, the latter representing a form of acquired glycogenic hepatopathy.

  14. Prevalence of hepatopathy in type 1 diabetic children

    Directory of Open Access Journals (Sweden)

    Al-Hussaini Abdulrahman A

    2012-10-01

    Full Text Available Abstract Background The Prevalence of liver disease among diabetics has been estimated to be between 17% and 100%. Most of these data were obtained from adult studies. The aim of our study was to screen for liver disease among type 1 diabetic children. Methods Children with type 1 diabetes following in clinic have been examined for existence of liver disease, from November 2008 to November 2009. All were subjected to the following: History, physical examination, liver function tests, fasting lipid profile, HbA1C, and ultrasound of the liver. A hyperechogenic liver and/or hepatomegaly on ultrasound were attributed most likely to excess glycogen or fat in the liver, after negative extensive work-up to rule out other underlying liver disease. Results 106 children with type 1 diabetes were studied: age ranged between 8 months to 15.5 years, sixty two patients were females. Twenty two patients (21% were identified to have abnormal findings on ultrasound of the liver: 10 patients had hepatomegaly and 12 had hyperechogenic liver. The group with hyperechogenic liver had poorer glycemic control than patients with normal liver (Mean HbA1c 12.14% Vs 10.7%; P value = 0.09. Hyperechogenic liver resolved in 60% at 6 months follow-up upon achieving better glycemic control. Conclusions Hyperechogenic liver and/or hepatomegaly are not uncommon in children with type 1 diabetes and tend to be more prevalent among children with poor glycemic control. Type 1 diabetes related hepatopathy is reversible by optimizing glycemic control. Because of its safety, and reliability, ultrasound can be used to screen for hepatopathy in type 1 diabetic child.

  15. A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression

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    María de la Luz García-Hernández

    2017-05-01

    Full Text Available ObjectiveMultiple solid cancers contain tertiary lymphoid organs (TLO. However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function.MethodsWe used multicolor immunofluorescence to stain prostate tissues, collected at different stages of cancer progression (prostatic intraepithelial neoplasia, intermediate and advanced cancer or from patients with evanescent prostate carcinoma. Tissues were stained with antibodies specific for pro-inflammatory molecules (cyclooxygenase 2, CXCL10, IL17, tumor-infiltrating immune cells (mature DC-LAMP+ dendritic cells, CD3+ T cells, CD3+Foxp3+ regulatory T cells (Treg, T bet+ Th1 cells, granzyme B+ cytotoxic cells, and stromal cell populations (lymphatic vessels, tumor neovessels, high endothelial venules (HEV, stromal cells, which promote prostate tumor growth or are critical components of tumor-associated TLO.ResultsGenerally, inflammatory cells are located at the margins of tumors. Unexpectedly, we found TLO within prostate tumors from patients at different stages of cancer and in unique samples from patients with spontaneous cancer remission. In evanescent prostate carcinomas, accumulation of Treg was compromised, while Tbet+ T cells and CD8 T cells were abundant in tumor-associated TLO. In addition, we found a global decrease in tumor neovascularization and the coverage by cells positive for cyclooxygenase 2 (COX2. Finally, consistent with tumor regression, prostate stem cell antigen was

  16. Does disease-irrelevant intrathecal synthesis in multiple sclerosis make sense in the light of tertiary lymphoid organs?

    Science.gov (United States)

    Bonnan, Mickael

    2014-01-01

    Although partly disease-irrelevant, intrathecal immunoglobulins (Ig) synthesis is a typical feature of multiple sclerosis (MS) and is driven by the tertiary lymphoid organs (TLO). A long-known hallmark of this non-specific intrathecal synthesis is the MRZ pattern, an intrathecal synthesis of Ig against measles, rubella, and zoster viruses. This non-specific intrathecal synthesis could also be directed against a wide range of pathogens. However, it is highly problematic since brain TLO should not be able to drive the clonal expansion of lymphocytes against alien antigens that are thought to be absent in MS brain. We propose to explain the paradox of non-specific intrathecal synthesis by discussing the natural properties of TLO. In fact, besides local antigen-driven clonal expansion, circulating plasmablasts and plasma cells (PC) are non-specifically recruited from blood and gain access to survival niches in the inflammatory CNS. This mechanism, which has been described in other inflammatory disorders, takes place in the TLO. As a consequence, PCs recruited in brain mirror the individual's history of immunization and intrathecal synthesis of IgG in MS may target a broad range of common infectious agents, a hypothesis in line with epidemiological data. Moreover, the immunization schedule and its timing may interfere with PC recruitment. If this hypothesis is correct, the reaction against EBV appears paradoxical: although early infection of MS patients is systematic, intrathecal synthesis is far lower than expected, suggesting a crucial interaction between MS onset and timing of EBV infection. A growing body of evidence suggests that the non-specific intrathecal synthesis observed in MS is also common in many chronic CNS inflammatory disorders. Assuming that cortical TLO in MS are associated with typical sub-pial lesions, we have coined the concept of "TLO-pathy" to describe these lesions and take examples of them from non-MS disorders. Lastly, we propose that

  17. Characterization of B and plasma cells in blood, bone marrow, and secondary lymphoid organs of rhesus macaques by multicolor flow cytometry.

    Science.gov (United States)

    Neumann, Berit; Klippert, Antonina; Raue, Katharina; Sopper, Sieghart; Stahl-Hennig, Christiane

    2015-01-01

    B cells, as an important part of the humoral immune response, are generated in the BM, migrate to secondary lymphoid organs, and upon activation, differentiate into antibody-producing memory B cells or plasma cells. Despite the pivotal roles that they play in different diseases, a comprehensive characterization in healthy rhesus macaques, which serve as valuable models for a variety of human diseases, is still missing. With the use of multiparameter flow cytometry, we analyzed B cells in BM collected from two locations, i.e., the iliac crest (BMca) and the femur (BMfem), PB, as well as secondary lymphoid organs of healthy rhesus macaques. We assessed the frequencies of immature and mature B cells, as well as CD19(+) CD20(-) CD38(+/++) CD138(+/++) plasmablasts/plasma cells. Furthermore, we found site-specific differences in the expression of markers for B cell activation and proliferation, chemokine receptors and Igs, as well as the distribution of memory B cell subpopulations. As secondary lymphoid organs harbor the highest frequencies of naive B cells, expression of CD80, CD95, and Ki67 was lower compared with B cells in the periphery and BM, whereas expression of IgD, CXCR4 (CD184), and CCR7 (CD197) was higher. Interestingly, BMca differed from BMfem regarding frequencies of B cells, their expression of CD80 and CXCR4, T cells, and plasma cells. In summary, these data identify baseline values for the above-mentioned parameters and provide the foundation for future studies on B and plasma cells in different diseases.

  18. HIV-1 infected lymphoid organs upregulate expression and release of the cleaved form of uPAR that modulates chemotaxis and virus expression.

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    Manuela Nebuloni

    Full Text Available Cell-associated receptor for urokinase plasminogen activator (uPAR is released as both full-length soluble uPAR (suPAR and cleaved (c-suPAR form that maintain ability to bind to integrins and other receptors, thus triggering and modulating cell signaling responses. Concerning HIV-1 infection, plasma levels of suPAR have been correlated with the severity of disease, levels of immune activation and ineffective immune recovery also in individuals receiving combination anti-retroviral therapy (cART. However, it is unknown whether and which suPAR forms might contribute to HIV-1 induced pathogenesis and to the related state of immune activation. In this regard, lymphoid organs represent an import site of chronic immune activation and virus persistence even in individuals receiving cART. Lymphoid organs of HIV-1(+ individuals showed an enhanced number of follicular dendritic cells, macrophages and endothelial cells expressing the cell-associated uPAR in comparison to those of uninfected individuals. In order to investigate the potential role of suPAR forms in HIV-1 infection of secondary lymphoid organs, tonsil histocultures were established from HIV-1 seronegative individuals and infected ex vivo with CCR5- and CXCR4-dependent HIV-1 strains. The levels of suPAR and c-suPAR were significantly increased in HIV-infected tonsil histocultures supernatants in comparison to autologous uninfected histocultures. Supernatants from infected and uninfected cultures before and after immunodepletion of suPAR forms were incubated with the chronically infected promonocytic U1 cell line characterized by a state of proviral latency in unstimulated conditions. In the contest of HIV-conditioned supernatants we established that c-suPAR, but not suPAR, inhibited chemotaxis and induced virus expression in U1 cells. In conclusion, lymphoid organs are an important site of production and release of both suPAR and c-suPAR, this latter form being endowed with the capacity of

  19. Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

    Directory of Open Access Journals (Sweden)

    Teruaki Toyota

    2012-01-01

    Full Text Available We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT, glutamic pyruvic transaminase (GPT in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  20. Clinicopathological, ultrasonographic, and histopathological findings of superficial necrolytic dermatitis with hepatopathy in a cat.

    Science.gov (United States)

    Kimmel, Susan E; Christiansen, Wendy; Byrne, Kevin P

    2003-01-01

    This report describes the antemortem diagnosis and antemortem and postmortem findings of superficial necrolytic dermatitis with hepatopathy (i.e., hepatocutaneous syndrome) in a cat. A 5-year-old Maine coon was evaluated because of a history of pruritic alopecia and liver enzyme elevations. Abdominal ultrasonography revealed a reticular pattern to the hepatic parenchyma. Histopathological findings of the liver were nodular regeneration with bands of vacuolated hepatocytes and bile duct hyperplasia, characteristic of the hepatopathy frequently associated with superficial necrolytic dermatitis. Skin histopathology revealed multifocal parakeratosis, midepidermal spongiosis, and basal cell hyperplasia consistent with superficial necrolytic dermatitis.

  1. Detection of Porcine Circovirus Type 2 and Viral Replication by In Situ Hybridization in Primary Lymphoid Organs From Naturally and Experimentally Infected Pigs

    DEFF Research Database (Denmark)

    Hansen, Mette Sif; Segalés, J.; Fernandes, L.;

    2013-01-01

    affected by PMWS (n = 33), and age-matched healthy control animals (n = 29). In situ hybridization (ISH) techniques were used to detect PCV2 nucleic acid irrespective of replicative status (complementary probe, CP) or to detect only the replicative form of the virus (replicative form probe, RFP). PCV2...... was not detected in the experimentally PCV2-inoculated pigs or the control animals. Among the PMWS-affected pigs, 19 of 20 (95%) thymuses were positive for PCV2 by CP ISH, and 7 of 19 (37%) of these also supported viral replication. By CP ISH, PCV2 was detected in 16 of 33 (48%) bone marrow samples, and 5 of 16...... of PMWS. The aim of this study was to determine if primary lymphoid organ cells support viral replication during PCV2 infection. This was done by histopathological examination of thymus and bone marrow from pigs experimentally inoculated with PCV2 (n = 24), mock-infected pigs (n = 12), pigs naturally...

  2. Glycogenic hepatopathy, an underdiagnosed cause of relapsing hepatitis in uncontrolled type 1 diabetes mellitus

    Science.gov (United States)

    Sarkhy, Ahmed A. Al; Zaidi, Zafar A.; Babiker, Amir M.

    2017-01-01

    Glycogenic hepatopathy is a rare condition that causes significant hepatomegaly and elevated liver enzyme levels in uncontrolled type 1 diabetic patients. It develops due to excessive accumulation of glycogen in the hepatocytes. It is typically reversible with good glycemic control and rarely progresses to mild fibrosis, but not cirrhosis. PMID:28042636

  3. Immunohistochemical evidences showing the presence of thymulin containing cells located in involuted thymus and in peripheral lymphoid organs.

    Science.gov (United States)

    Folch, Hugo; Villegas, Juana V; Leyan, Víctor; Barría, Miguel; Eller, Gisela; Esquivel, Patricio

    2010-01-01

    Thymulin is a well-characterized thymic hormone that exists as a nonapeptide coupled to equimolar amounts of Zn2+. Thymulin is known to have multiple biological roles, including T cell differentiation, immune regulation, and analgesic functions. It has been shown that thymulin is produced by the reticulo-epithelial cells of the thymus, and it circulates in the blood from the moment of birth, maintain its serum level until puberty diminishing thereafter in life. To study the localization of this hormone, we prepared polyclonal and monoclonal antibodies against the commercial peptide and utilized immunocytochemical techniques for visualization. The results indicate that thymulin stains the thymic reticular cells, the outer layers of Hassall's corpuscles and a large round cellular type, which is keratin-negative and does not show affinity for the common leukocyte antigen (CD-45). In mice, this thymulin-positive cell remains in the thymus throughout life and even appears in relatively increased numbers in old involuted thymi. It also appears in thymus-dependent areas of the spleen and lymph nodes, demonstrating that at least one of the thymus cells containing this peptide can be found in peripheral lymphoid tissue.

  4. Dynamics of Lymphocyte Populations during Trypanosoma cruzi Infection: From Thymocyte Depletion to Differential Cell Expansion/Contraction in Peripheral Lymphoid Organs

    Directory of Open Access Journals (Sweden)

    Alexandre Morrot

    2012-01-01

    Full Text Available The comprehension of the immune responses in infectious diseases is crucial for developing novel therapeutic strategies. Here, we review current findings on the dynamics of lymphocyte subpopulations following experimental acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. In the thymus, although the negative selection process of the T-cell repertoire remains operational, there is a massive thymocyte depletion and abnormal release of immature CD4+CD8+ cells to peripheral lymphoid organs, where they acquire an activated phenotype similar to activated effector or memory T cells. These cells apparently bypassed the negative selection process, and some of them are potentially autoimmune. In infected animals, an atrophy of mesenteric lymph nodes is also observed, in contrast with the lymphocyte expansion in spleen and subcutaneous lymph nodes, illustrating a complex and organ specific dynamics of lymphocyte subpopulations. Accordingly, T- and B-cell activation is seen in subcutaneous lymph nodes and spleen, but not in mesenteric lymph nodes. Lastly, although the function of peripheral CD4+CD8+ T-cell population remains to be defined in vivo, their presence may contribute to the immunopathological events found in both murine and human Chagas disease.

  5. Effect of free-range days on a local chicken breed: growth performance, carcass yield, meat quality, and lymphoid organ index.

    Science.gov (United States)

    Tong, H B; Wang, Q; Lu, J; Zou, J M; Chang, L L; Fu, S Y

    2014-08-01

    An experiment was conducted to evaluate the effect of free-range days on growth performance, carcass yield, meat quality, and lymphoid organ index of a local chicken breed. In total, 1,000 one-day-old male Suqin yellow chickens were raised for 21 d. On d 21, 720 birds with similar BW (536 ± 36 g) were selected and randomly assigned to free-range treatment at 21, 28, 35, and 42 d of age (assigned to free-range treatment for 21, 14, 7, and 0 d, respectively). Each treatment was represented by 5 replicates (pens) containing 36 birds (180 birds per treatment). All the birds were raised in indoor floor pens measuring 1.42 × 1.42 m (2 m(2), 18 birds/m(2)) in conventional poultry research houses before free-range treatment. In the free-range treatment, the chickens were raised in indoor floor houses measuring 3 × 5 m (15 m(2), 2.4 birds/m(2)). In addition, they also had an outdoor free-range paddock measuring 3 × 8 m (24 m(2), 1.5 birds/m(2)). The BW of birds after being assigned to free-range treatment for 7 d decreased significantly compared with that in the conventional treatment (P 0.05). The daily weight gain, feed per gain, daily feed intake, and mortality from 21 to 42 d of age were unaffected by free-range days (P > 0.05). At 42 d of age, the breast yield increased linearly with increasing free-range days (P 0.05). The absolute thymus weight and thymus:BW ratio showed a significant increasing and then decreasing quadratic response to increasing free-range days (P < 0.05). The findings of this study suggest that increasing free-range days advantageously affects breast yield, but decreases thigh, leg, thigh bone, and foot yields as well as the water-holding capacity of thigh. No evidence was found that increasing free-range days caused changes in growth performance, meat quality, and lymphoid organs except for changes in water-holding capacity and thymus. © Poultry Science Association Inc.

  6. CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph.

    Science.gov (United States)

    Carrega, Paolo; Bonaccorsi, Irene; Di Carlo, Emma; Morandi, Barbara; Paul, Petra; Rizzello, Valeria; Cipollone, Giuseppe; Navarra, Giuseppe; Mingari, Maria Cristina; Moretta, Lorenzo; Ferlazzo, Guido

    2014-04-15

    As limited information is available regarding the distribution and trafficking of NK cells among solid organs, we have analyzed a wide array of tissues derived from different human compartments. NK cells were widely distributed in most solid tissues, although their amount varied significantly depending on the tissue/organ analyzed. Interestingly, the distribution appeared to be subset specific, as some tissues were preferentially populated by CD56(bright)perforin(low) NK cells, with others by the CD56(dim)perforin(high) cytotoxic counterpart. Nevertheless, most tissues were highly enriched in CD56(bright)perforin(low) cells, and the distribution of NK subsets appeared in accordance with tissue gene expression of chemotactic factors, for which receptors are differently represented in the two subsets. Remarkably, chemokine expression pattern of tissues was modified after neoplastic transformation. As a result, although the total amount of NK cells infiltrating the tissues did not significantly change upon malignant transformation, the relative proportion of NK subsets infiltrating the tissues was different, with a trend toward a tumor-infiltrating NK population enriched in noncytotoxic cells. Besides solid tissues, CD56(bright)perforin(low) NK cells were also detected in seroma fluids, which represents an accrual of human afferent lymph, indicating that they may leave peripheral solid tissues and recirculate to secondary lymphoid organs via lymphatic vessels. Our results provide a comprehensive mapping of NK cells in human tissues, demonstrating that discrete NK subsets populate and recirculate through most human tissues and that organ-specific chemokine expression patterns might affect their distribution. In this context, chemokine switch upon neoplastic transformation might represent a novel mechanism of tumor immune escape.

  7. Synoptic tool for reporting of hematological and lymphoid neoplasms based on World Health Organization classification and College of American Pathologists checklist

    Directory of Open Access Journals (Sweden)

    Winters Sharon B

    2007-07-01

    Full Text Available Abstract Background Synoptic reporting, either as part of the pathology report or replacing some free text component incorporates standardized data elements in the form of checklists for pathology reporting. This ensures the pathologists make note of these findings in their reports, thereby improving the quality and uniformity of information in the pathology reports. Methods The purpose of this project is to develop the entire set of elements in the synoptic templates or "worksheets" for hematologic and lymphoid neoplasms using the World Health Organization (WHO Classification and the College of American Pathologists (CAP Cancer Checklists. The CAP checklists' content was supplemented with the most updated classification scheme (WHO classification, specimen details, staging as well as information on various ancillary techniques such as cytochemical studies, immunophenotyping, cytogenetics including Fluorescent In-situ Hybridization (FISH studies and genotyping. We have used a digital synoptic reporting system as part of an existing laboratory information system (LIS, CoPathPlus, from Cerner DHT, Inc. The synoptic elements are presented as discrete data points, so that a data element such as tumor type is assigned from the synoptic value dictionary under the value of tumor type, allowing the user to search for just those cases that have that value point populated. Results These synoptic worksheets are implemented for use in our LIS. The data is stored as discrete data elements appear as an accession summary within the final pathology report. In addition, the synoptic data can be exported to research databases for linking pathological details on banked tissues. Conclusion Synoptic reporting provides a structured method for entering the diagnostic as well as prognostic information for a particular pathology specimen or sample, thereby reducing transcription services and reducing specimen turnaround time. Furthermore, it provides accurate and

  8. Effect of Prevention and Treatment of Murine Acute Viral Myocarditisand Protection of Lymphoid Organ Atrophy withXinkang Oral Liquid (心康口服液)

    Institute of Scientific and Technical Information of China (English)

    万素君; 赵红; 李建农; 王丽霞; 黄霞珍; 陈鸿珊

    2002-01-01

    Objective:The effect of prevention and treatment of Xinkang oral liquid (心康口服液, XKOL) on experimental coxsackievirus B 3 (CVB 3) myocarditis mice model were investigated. Methods: The mice were inoculated intrap eritoneally with 0.3 ml of 10 5 TCID 50 of CVB 3 to in duce acute viral myocarditis model. These mice were divided into model control group (Group A), prevention high do sage group (Group B) and prevention low dosage grou p (Group C), treatment high dosage group (Group D) and treatm ent low dosage group (Group E), respectively. In addition, XKOL control group (Group F) and normal control grou p (Group G) were not infected with CVB 3 intraperitoneally. The administration of XKOL in Group B a nd C began 2 days before virus infection. All animals were sacrificed on day 20 for evaluation. Results: Histological examination showed extensive m yocardial necrosis and cell infiltration in most of Group A mice, but necrosis and cell infiltration were less severe in Group B,C,D and E mice. Thymus weight in Group B,C,D and E mice were heavier and less cell depletion occurred than those in Group A. Conclussion: The XKOL could effectively inhibit myoc ardial CVB 3 replication, reduce the myocardial inflammatory response, lower incidence rate of myocarditis and prevent the disease associated lymphoid organ atrophy in this animal models.

  9. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Martinelli, Diego [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Dionisi-Vici, Carlo [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Nobili, Valerio [Gastroenterology and Liver Unit, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Francalanci, Paola; Boldrini, Renata; Callea, Francesco [Dept. Pathology, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Santorelli, Filippo Maria [UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); and others

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  10. [Morphological characteristics of the lymphoid tissues in the newborn children].

    Science.gov (United States)

    Aminova, G G; Grigorenko, D E; Rusina, A K; Erofeeva, L M

    2000-01-01

    Quantitative and qualitative analysis and statistical processing of thymus, trachea, duodenum ileum, coecum and appendix in newborns demonstrated that by the moment of birth peripheral immunogenesis organs were not equally formed due to peculiarities of their function in postnatal ontogenesis. Lymphoid nodules were absent in tracheal mucosa and adjacent lymph nodes showed loss of lymphoid noules aswell. However intensive formation of lymphoid structures took place in the walls of the gut, especially large intestine. The appendix, lymphoid tissue of which was not, in fact, developed at all, made an exception.

  11. CCR7 guides migration of mesenchymal stem cell to secondary lymphoid organs: a novel approach to separate GvHD from GvL effect.

    Science.gov (United States)

    Li, Hong; Jiang, YanMing; Jiang, XiaoXia; Guo, XiMin; Ning, HongMei; Li, YuHang; Liao, Li; Yao, HuiYu; Wang, XiaoYan; Liu, YuanLin; Zhang, Yi; Chen, Hu; Mao, Ning

    2014-07-01

    Inefficient homing of systemically infused mesenchymal stem cells (MSCs) limits the efficacy of existing MSC-based clinical graft-versus-host disease (GvHD) therapies. Secondary lymphoid organs (SLOs) are the major niches for generating immune responses or tolerance. MSCs home to a wide range of organs, but rarely to SLOs after intravenous infusion. Thus, we hypothesized that targeted migration of MSCs into SLOs may significantly improve their immunomodulatory effect. Here, chemokine receptor 7 (CCR7) gene, encoding a receptor that specifically guides migration of immune cells into SLOs, was engineered into a murine MSC line C3H10T1/2 by retrovirus transfection system (MSCs/CCR7). We found that infusion of MSCs/CCR7 potently prolonged the survival of GvHD mouse model. The infused MSCs/CCR7 migrate to SLOs, relocate in proximity with T lymphocytes, therefore, potently inhibited their proliferation, activation, and cytotoxicity. Natural killer (NK) cells contribute to the early control of leukemia relapse. Although MSCs/CCR7 inhibited NK cell activity in vitro coculture, they did not impact on the proportion and cytotoxic capacities of NK cells in the peripheral blood of GvHD mice. In an EL4 leukemia cell loaded GvHD model, MSCs/CCR7 infusion preserved the graft-versus-leukemia (GvL) effect. In conclusion, this study demonstrates that CCR7 guides migration of MSCs to SLOs and thus highly intensify their in vivo immunomodulatory effect while preserving the GvL activity. This exciting therapeutic strategy may improve the clinical efficacy of MSC based therapy for immune diseases.

  12. Mycolactone diffuses from Mycobacterium ulcerans-infected tissues and targets mononuclear cells in peripheral blood and lymphoid organs.

    Directory of Open Access Journals (Sweden)

    Hui Hong

    Full Text Available BACKGROUND: Buruli ulcer (BU is a progressive disease of subcutaneous tissues caused by Mycobacterium ulcerans. The pathology of BU lesions is associated with the local production of a diffusible substance, mycolactone, with cytocidal and immunosuppressive properties. The defective inflammatory responses in BU lesions reflect these biological properties of the toxin. However, whether mycolactone diffuses from infected tissues and suppresses IFN-gamma responses in BU patients remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here we have investigated the pharmacodistribution of mycolactone following injection in animal models by tracing a radiolabeled form of the toxin, and by directly quantifying mycolactone in lipid extracts from internal organs and cell subpopulations. We show that subcutaneously delivered mycolactone diffused into mouse peripheral blood and accumulated in internal organs with a particular tropism for the spleen. When mice were infected subcutaneously with M. ulcerans, this led to a comparable pattern of distribution of mycolactone. No evidence that mycolactone circulated in blood serum during infection could be demonstrated. However, structurally intact toxin was identified in the mononuclear cells of blood, lymph nodes and spleen several weeks before ulcerative lesions appear. Importantly, diffusion of mycolactone into the blood of M. ulcerans-infected mice coincided with alterations in the functions of circulating lymphocytes. CONCLUSION: In addition to providing the first evidence that mycolactone diffuses beyond the site of M. ulcerans infection, our results support the hypothesis that the toxin exerts immunosuppressive effects at the systemic level. Furthermore, they suggest that assays based on mycolactone detection in circulating blood cells may be considered for diagnostic tests of early disease.

  13. Lymphoid Tissue and Pathological Influences of Toxicants

    NARCIS (Netherlands)

    Schaudien, D.; Harleman, H.; Bouallala, F.; Kuper, C. F.

    2014-01-01

    Toxicologic pathology plays a crucial role in the identification and interpretation of substance-induced health effects. Histology of lymphoid organs is quite sensitive, although it does not flag every model immunotoxic substance. Subtle interferences of toxic compounds, like transmembrane signaling

  14. Mapping of NKp46+ cells in healthy human lymphoid and non-lymphoid tissues

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    Elena eTomasello

    2012-11-01

    Full Text Available Understanding Natural Killer (NK cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs expressing the retinoic acid receptor-related orphan receptor t (RORt transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORt+ILCs with a lineage-CD94-CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.

  15. Betaine: a potential agent for the treatment of hepatopathy associated with short bowel syndrome

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    Guilherme Teixeira Araújo

    2014-06-01

    Full Text Available Background: The hepatopathy associated with short bowel syndrome (SBS is a multifactorial disease associated with poor prognosis. Besides intestinal transplantation, no other treatment has been shown effective. The current study evaluated the efficacy of betaine for the treatment of hepatopathy associated with SBS. Methods: A prospective, unicentric, non-placebo controlled trial was carried out. After initial evaluation, 10g of betaine anhydrous was administrated to SBS patients in two divided doses for three months. The hepatic steatosis was assessed through nuclear magnetic resonance (NMR, the inflammatory response by interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α and ferritin, besides the hepatic lesion through hepatic enzymes and bilirubin. Furthermore, the effect of betaine on homocysteine was evaluated as well as its safety and tolerability in this group of patients. Results: After three months supplementation, patients showed decreased percentage of hepatic fat (p = 0.03 through triphasic NMR examination. There was no significant reduction of serum levels for inflammatory proteins and hepatic lesion markers. Homocysteinemia also did not present significant decrease. The most prevalent side effects were diarrhea and nausea, reported in 62% of the participants; however, these symptoms were transient and not severe enough to justify the treatment interruption. Parenteral nutrition-dependent patients did not present different hepatic lesion degree compared to patients who do not need the prolonged use of it. Conclusions: Betaine was shown to be a potential agent for the treatment of hepatopathy associated with SBS, which was evidenced by NMR, although the markers for hepatic lesion have not presented significant decrease.

  16. Upregulation of CC Chemokine Receptor 7 (CCR7) Enables Migration of Xenogeneic Human Adipose-Derived Mesenchymal Stem Cells to Rat Secondary Lymphoid Organs.

    Science.gov (United States)

    Ma, Tian; Luan, Shao-Liang; Huang, Hong; Sun, Xing-Kun; Yang, Yan-Mei; Zhang, Hui; Han, Wei-Dong; Li, Hong; Han, Yan

    2016-12-30

    BACKGROUND CC chemokine receptor 7 (CCR7) expression is vital for cell migration to secondary lymphoid organs (SLOs). Our previous work showed that inducing CCR7 expression enabled syngeneic mesenchymal stem cells (MSCs) to migrate into SLOs, resulting in enhanced immunosuppressive performance in mice. Given that human adipose-derived stem cells (hASCs) are widely used in clinical therapy, we further investigated whether upregulation of CCR7 enables xenogeneic hASCs to migrate to rat SLOs. MATERIAL AND METHODS hASCs rarely express CCR7; therefore, hASCs were transfected with lentivirus encoding rat CCR7 (rCCR7) plus green fluorescence protein (GFP) or GFP alone. CCR7 mRNA and cell surface expression of rCCR7-hASCs and GFP-hASCs were examined by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FCM), respectively. The phenotype, differentiation, and proliferation capacity of each cell type was also determined. To examine migration, rCCR7-hASCs and GFP-hASCs were injected intravenously into Lewis rats, and the proportion of GFP-positive cells in the spleen and lymph nodes was determined with FCM. RESULTS mRNA and cell surface protein expression of CCR7 was essentially undetectable in hASCs and GFP-ASCs; however, CCR7 was highly expressed in rCCR7-ASCs. rCCR7-hASCs, GFP-hASCs, and hASCs shared a similar immunophenotype, and maintained the ability of multilineage differentiation and proliferation. In addition, the average proportion of GFP-positive cells was significantly higher following transplantation of rCCR7-hASCs compared with GFP-hASCs (p<0.01). CONCLUSIONS These results suggest that upregulation of rat CCR7 expression does not change the phenotype, differentiation, or proliferation capacity of hASCs, but does enable efficient migration of hASCs to rat SLOs.

  17. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

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    Federica Marchesi

    2011-12-01

    Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  18. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

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    Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

    2011-12-28

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  19. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs.

  20. Role of lymphotoxin and homeostatic chemokines in the development and function of local lymphoid tissues in the respiratory tract.

    Science.gov (United States)

    Rangel-Moreno, Javier; Carragher, Damian; Randall, Troy D

    2007-01-01

    Secondary lymphoid organs are strategically placed to recruit locally activated antigen presenting cells (APCs) as well as naïve, recirculating T and B cells. The structure of secondary lymphoid organs - separated B and T zones, populations of specialized stromal cells, high endothelial venules and lymphatic vessles - has also evolved to maximize encounters between APCs and lymphocytes and to facilitate the expansion and differentiation of antigen-stimulated T and B cells. Many of the general mechanisms that govern the development and organization of secondary lymphoid organs have been identified over the last decade. However, the specific cellular and molecular interactions involved in the development and organization of each secondary lymphoid organ are slightly different and probably reflect the cell types available at that time and location. Here we review the mechanisms involved in the development, organization and function of local lymphoid tissues in the respiratory tract, including Nasal Associated Lymphoid Tissue (NALT) and inducible Bronchus Associated Lymphoid Tissue (iBALT).

  1. Effects of outdoor access days on growth performance, carcass yield, meat quality, and lymphoid organ index of a local chicken breed.

    Science.gov (United States)

    Tong, H B; Cai, J; Lu, J; Wang, Q; Shao, D; Zou, J M

    2015-06-01

    An experiment was conducted to evaluate the effect of outdoor access days on growth performance, carcass yield, meat quality, and lymphoid organ index of a local chicken breed. In total, 864 twenty one-day-old male Suqin yellow chickens, with similar body weight (536±36g), were selected and raised in indoor floor pens that measured 1.42×1.42 m (2 m2, 18 birds/m2) in conventional poultry research houses (36 birds per pen). Two hundred and sixteen birds were allowed outdoor access treatments at 21, 28, 35, and 42 d of age, respectively (access to outdoor for 35, 28, 21, and 14 days, respectively). Each treatment was represented by 6 replicates (pens) containing 36 birds (216 birds per treatment). In the outdoor access treatment, the birds had an outdoor free-range paddock that measured 3×8 m (24 m2, 1.5 birds/m2). The body weight of birds at 56 d of age increased linearly with increasing outdoor access days (P<0.001), but there was no effect of the outdoor access days on the body weight at 42 d of age (P=0.161). The daily weight gain, daily feed intake, and feed per gain from 21 to 42 d of age were unaffected by outdoor access days (P=0.401, P=0.463, P=0.223, respectively). However, the daily weight gain and daily feed intake from 42 to 56 and from 21 to 56 d of age increased linearly with increasing outdoor access days (P=0.002, P<0.001; P=0.001, P=0.004; respectively), while the feed per gain tended to decrease linearly from 21 to 56 d of age (P=0.060). The mortality from 21 to 56 d of age was unaffected by outdoor access days (P=0.261). At 56 d of age, the breast yield increased linearly with increasing outdoor access days (P<0.001), while the foot yield decreased linearly (P=0.016). The light (L*) and red (b*) values of leg meat color increased linearly with increasing outdoor access days (P=0.032, P=0.013, respectively). The spleen: the body weight ratio showed a decreasing and then increasing quadratic response to increasing outdoor access days (P=0

  2. Simian Immunodeficiency Virus Targeting of CXCR3(+) CD4(+) T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

    Science.gov (United States)

    Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A; Villinger, Francois; Mori, Kazuyasu

    2017-07-01

    Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4(+) T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4(+) T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3(+) CCR5(+) CD4(+) T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3(+) T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14(+) CD16(+) monocytes and MAC387(+) macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387(+) macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages.IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4(+) T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G

  3. Expression of gene, protein and immunohistochemical localization of the estrogen receptor isoform ERα1 in male rainbow trout lymphoid organs; indication of the role of estrogens in the regulation of immune mechanisms.

    Science.gov (United States)

    Massart, Sophie; Milla, Sylvain; Kestemont, Patrick

    2014-08-01

    In vertebrates, estrogens act on the reproductive system but also affect the functioning of non-reproductive tissues such as the immune system. In teleost fish, effects of estrogens and xenoestrogens have been reported extensively, but the available information on targeted tissues and cells is still scarce. Moreover, a better knowledge of the distinct ER subtypes is required to find out the mechanistic pathways by which estrogen compounds are able to disrupt endogenous estrogen signaling in fish immunity. The present study aimed at characterizing, in male rainbow trout juveniles, multi-tissue gene expression pattern of one isoform of estrogen receptor (ER), ERα1, at the mRNA and protein levels. The mRNA levels for ERα1 were measured in various lymphoid organs by real-time RT-PCR and ERα1 protein level by Western blot. Furthermore, this protein was located by immunohistochemistry in the same organs. The transcripts were ubiquitously expressed, but at a higher level in testis and liver, while the protein was more abundant in testis and skin. Moreover, the ERα1 was detected in endothelial, Kupffer, mucous and chloride cells, hematopoietic tissues, proximal tubule, epithelia of the skin and intestine, in the lamina propria and in the stratum granulosum. This distribution backs the idea that, in male rainbow trout, estrogeno-mimetic compounds could be involved in different immune mechanisms such as inflammatory response, transport of Ig, mucus production, regulation of cellular immunity and development and maturation of lymphoid and myeloid cells.

  4. Blood microvascular organization of the nasal-associated lymphoid tissue of the guinea pig: a scanning electron microscopic study of corrosion casts.

    Directory of Open Access Journals (Sweden)

    Okada,Satoko

    1995-08-01

    Full Text Available It has previously been confirmed that the guinea pig has aggregations of 10-20 lymphoid follicles at the junction of the nasal cavity and the nasopharyngeal duct. The vascular architecture of this nasal-associated lymphoid tissue (NALT was studied by the corrosion cast/scanning electron microscope method. The NALT was supplied by branches of the inferior nasal artery. These afferent arterial branches gave off arterioles to the follicles and the interfollicular regions, where the arterioles ramified into capillaries. Some of these arterioles reached the subepithelial region to form a single-layer dense capillary network. The subepithelial capillaries gathered into short collecting venules, which in turn drained into high endothelial venules (HEV in the interfollicular region. The HEV, which also receives tributaries from the follicular and interfollicular capillary plexuses, descended in the interfollicular regions and finally flowed into the efferent veins at the bottom of the NALT. Indentations impressed by high endothelial cells (HEC were prominent on the surface of the HEV casts, and their frequency was larger in the upper course or segments than in the lower. This suggests that the incidence of HEC in the upper segments is higher than in the lower segments, and these findings are consistent with the hypothesis that some substances which are taken up into the subepithelial capillaries and transported to the venules induce differentiation and maintain of HEVs.

  5. The Innate Lymphoid Cell Precursor.

    Science.gov (United States)

    Ishizuka, Isabel E; Constantinides, Michael G; Gudjonson, Herman; Bendelac, Albert

    2016-05-20

    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages.

  6. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.

  7. Age-related changes and distribution of T cell markers (CD3 and CD4) and toll-like receptors(TLR2, TLR3,TLR4 and TLR7) in the duck lymphoid organs.

    Science.gov (United States)

    Zhang, Aiguo; Xu, Jiahua; Lai, Hanzhang; Huang, Wenke; Fang, Niran; Chen, Ruiai

    2017-03-10

    T lymphocytes and Toll-like receptors have been confirmed to have correlation with the ability to resistance to pathogenic challenges and play an important role in duck immune system. However, the information of ontogeny of T lymphocytes and Toll-like receptors is scarcely in duck. Therefore, to address these questions, we report the development and distribution of CD3 and CD4 by immunocytochemistry and the age-related mRNA level of duck T cell markers (CD3 and CD4) and Toll-like receptors (TLR2, TLR3, TLR4 and TLR7) by real time quantitative PCR in duck lymphoid organs (thymus, bursa of Fabricius and spleen). Results indicated that CD3 and CD4 positive cells can be observed in all test organs and partly change in an age-related way. CD4 positive T cell of duck spleen mainly distributed in periarterial lymphatic sheaths and red pulp, not in white pulp. Both of CD3 and CD4 were experienced significant increased wave twice in duck lymphoid organs and T cell dependent cellular immunity of duck may well established until 5 weeks old. The mRNA expression levels of duck TLRs were age and organ dependent, and duck TLR3 and TLR7 were significantly lower abundance in the spleen but higher in thymus and bursa of Fabricius, respectively. This study provide the essential knowledge of the ontogeny of T cells and Toll-like receptors in duck, which may shed lights on the T-cell mediate immunity and innate immunity in duck.

  8. An optimized protocol for isolating lymphoid stromal cells from the intestinal lamina propria.

    Science.gov (United States)

    Stzepourginski, Igor; Eberl, Gérard; Peduto, Lucie

    2015-06-01

    Mesenchymal stromal cells in lymphoid organs, also called lymphoid stromal cells (LSCs), play a pivotal role in immunity by forming specialized microenvironments that provide signals for leukocyte migration, positioning, and survival. Best characterized in lymphoid organs, LSCs are also abundant in the intestinal mucosa, which harbors a rich repertoire of immune cells. However, the lack of efficient procedures for isolation and purification of LSCs from the intestine has been a major limitation to their characterization. Here we report a new method to efficiently isolate, in addition to immune cells, viable lymphoid stromal cells and other stromal subsets from the intestinal lamina propria for subsequent phenotypic and functional analysis.

  9. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  10. Effect of dietary fiber in edible seaweeds on the development of D-galactosamine-induced hepatopathy in rats.

    Science.gov (United States)

    Kawano, Naoko; Egashira, Yukari; Sanada, Hiroo

    2007-10-01

    Previous studies in our laboratory demonstrated the repressive effect of seaweeds (Laminaria sp., Sargassum fulvellum, Eisenia bicyclis and Gelidium sp.) against D-galactosamine (D-GalN)-induced hepatopathy. However, the mechanism by which these four seaweeds attenuate the D-GalN-hepatopathy has not been completely clarified. This study was carried out to determine the constituents of these seaweeds that protect rats against the D-GalN-hepatopathy. Male Wistar rats were fed for 8 d diets containing 5% seaweeds with or without the antibiotic neomycin (NEO) in experiment 1, and typical seaweed dietary fibers (laminaran, fucoidan, alginate, agar and kappa-carrageenan) of these seaweeds in experiment 2. On the 7th day, the rats were treated with D-GalN (1,900 mg in experiment 1 and 800 mg/kg in experiment 2) and then sacrificed 24 h after the injection of D-GalN. Their serum transaminase (aspartate and alanine aminotransferases: AST and ALT) activities were then determined. In experiment 1, the serum AST and ALT levels in the rats fed the four kinds of seaweeds without NEO were significantly low in comparison to that of the control group, but those with NEO were not significantly different among the groups. In experiment 2, the serum AST and ALT levels in the rats fed fucoidan were significantly low in comparison to those of the other groups fed the dietary fibers and the control. These results suggest that the protective effect of the three kinds of brown seaweeds Laminaria sp., Sargassum fulvellum and Eisenia bicyclis against D-GalN-hepatopathy was caused at least in part by fucoidan.

  11. Combined Effect of Low-Intensity Helium-Neon Laser and X-Ray Radiation on in Vivo Cellular Response of the Whole Blood and Lymphoid Organs in Mice.

    Science.gov (United States)

    Zaichkina, S I; Dyukina, A R; Rozanova, O M; Romanchenko, S P; Sirota, N P; Kuznetsova, E A; Simonova, N B; Sorokina, S S; Zakrzhevskaya, D T; Yusupov, V I; Bagratishvili, V N

    2016-09-01

    We studied the effect of exposure to helium-neon laser (dose range 0.16-50 mJ/cm(2)) on activation of natural protection reserve in mice using the adaptive response test. DNA comets method revealed a protective response manifested in DNA damage level in whole blood leukocytes of mice and in lymphoid organs by the thymus and spleen weight index; preexposure to laser did not induce the adaptive response. ROS level in the whole blood was assessed by the level of zymosan-induced luminol chemiluminescence. In mice subjected to adaptive laser irradiation in doses of 0.16-5 mJ/cm(2) followed by X-ray irradiation in a dose of 1.5 Gy, the activation index calculated as the ratio of induced to spontaneous area of luminescence was by 1.4 times lower than that in non-irradiated animals, which attested to reduced ROSgeneration reserve capacity of neutrophils.

  12. Histopathology of mucosa-associated lymphoid tissue

    NARCIS (Netherlands)

    Kuper, C.F.

    2006-01-01

    Mucosa-associated lymphoid tissue (MALT) is a generalized term incorporating a disseminated collection of lymphoid tissues in multiple sites throughout the body. MALT sites that have been/are primarily studied include bronchus-associated lymphoid tissue (BALT), gut-associated lymphoid tissue (GALT),

  13. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans.

    Science.gov (United States)

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence.

  14. Expression of Toll-like receptors (TLR, in lymphoid organ of black tiger shrimp (Penaeus monodon in response to Vibrio harveyi infection

    Directory of Open Access Journals (Sweden)

    Mundanda Muthappa Dechamma

    2015-05-01

    Full Text Available The Toll-like receptors (TLR, being pattern recognition molecules, are a powerful first line of defense in response to pathogen invasion. They are known to play a crucial role in detecting and binding to the microbial molecule and triggering a non-specific immune response. Quantitative real time PCR (qPCR expression of the TLR gene was studied in healthy and Vibrio harveyi infected black tiger shrimp (Penaeus monodon. Lymphoid tissue expression of TLR in V. harveyi infected animals 24 h post injection showed statistically significant up regulation of the gene as compared to the control animals sham injected with phosphate buffered saline (PBS. The qPCR expression pattern of TLR at different time points in shrimp administered with the immunostimulant glucan for 6 days by oral feeding followed by challenge with V. harveyi showed statistically significant level at 48 h post bacterial challenge as compared to the control (immunostimulant treated animals sham injected with PBS. The novelty of the study is that it elicits the role of TLRs as important response proteins of the innate immune system in the shrimp.

  15. Anti-hepatotoxic potential of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental rodents

    Institute of Scientific and Technical Information of China (English)

    Ramesh Kr Gupta; Rajnish Kr Singh; Sudhansu Ranjan Swain; Talib Hussain; Chandana Venkateswara Rao

    2012-01-01

    Objective: To evaluate hepatoprotective potential of the methanolic extract of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental animals. Methods: In the present study, in- vivo hepatoprotective effect of 50% methanolic extract of Hedyotis corymbosa (HCE, 100 and 200 mg/kg body weight) was evaluated using experimental models D-Galactosamine (D-GalN) (200 mg/kg, body weight i.p.) induced hepatotoxicity in experimental animals. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), γ-glutamyl transferase (γ-GT) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Results: Obtained results demonstrated that the treatment with HCE signi-cantly (P<0.05-P<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, HCE signi-cantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that HCE attenuated the hepatocellular necrosis and led to reduction of in ammatory cells in-ltration. Conclusions: The results of this study strongly indicate the protective effect of HCE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scienti-cally support its traditional use.

  16. ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation.

    Science.gov (United States)

    Jansen, Eric J R; Timal, Sharita; Ryan, Margret; Ashikov, Angel; van Scherpenzeel, Monique; Graham, Laurie A; Mandel, Hanna; Hoischen, Alexander; Iancu, Theodore C; Raymond, Kimiyo; Steenbergen, Gerry; Gilissen, Christian; Huijben, Karin; van Bakel, Nick H M; Maeda, Yusuke; Rodenburg, Richard J; Adamowicz, Maciej; Crushell, Ellen; Koenen, Hans; Adams, Darius; Vodopiutz, Julia; Greber-Platzer, Susanne; Müller, Thomas; Dueckers, Gregor; Morava, Eva; Sykut-Cegielska, Jolanta; Martens, Gerard J M; Wevers, Ron A; Niehues, Tim; Huynen, Martijn A; Veltman, Joris A; Stevens, Tom H; Lefeber, Dirk J

    2016-05-27

    The V-ATPase is the main regulator of intra-organellar acidification. Assembly of this complex has extensively been studied in yeast, while limited knowledge exists for man. We identified 11 male patients with hemizygous missense mutations in ATP6AP1, encoding accessory protein Ac45 of the V-ATPase. Homology detection at the level of sequence profiles indicated Ac45 as the long-sought human homologue of yeast V-ATPase assembly factor Voa1. Processed wild-type Ac45, but not its disease mutants, restored V-ATPase-dependent growth in Voa1 mutant yeast. Patients display an immunodeficiency phenotype associated with hypogammaglobulinemia, hepatopathy and a spectrum of neurocognitive abnormalities. Ac45 in human brain is present as the common, processed ∼40-kDa form, while liver shows a 62-kDa intact protein, and B-cells a 50-kDa isoform. Our work unmasks Ac45 as the functional ortholog of yeast V-ATPase assembly factor Voa1 and reveals a novel link of tissue-specific V-ATPase assembly with immunoglobulin production and cognitive function.

  17. Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine

    Science.gov (United States)

    Iwasaki, Akiko; Kelsall, Brian L.

    2000-01-01

    We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment. By two-color in situ immunofluorescence, CD11b+ myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8α+ lymphoid DCs are present in the T cell–rich interfollicular region (IFR). DCs that lack expression of CD8α or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3α mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED. In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3α. These data support a distinct role for MIP-3α/CCR6 in recruitment of CD11b+ DCs toward the mucosal surfaces and for MIP-3β/CCR7 in attraction of CD8α+ DCs to the T cell regions. Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections. PMID:10770804

  18. Amount of cells of diffuse lymphoid tissue of uterine tube in women of different age groups

    Directory of Open Access Journals (Sweden)

    S.V. Shadlinskaya

    2010-06-01

    Full Text Available The aim of the investigation was to study the amount of lymphoid cells of diffuse lymphoid tissue of uterine tube in women of different age. The transverse sections of one-third of each part of uterine tube from 116 women (from newborn to senile age were studied. The sections were colored by gematoksilin-eosin, by van Gizon, by Brashe, azur-2-eosine, by Qrimelius. The amount of lymphoid cells of diffuse lymphoid tissue of uterine tube increased till the age of 16-20 and remained at high level further on till the age of 35. The quantity of lymphoid cells of diffuse lymphoid tissue of uterine tube changed according to the age and localization throughout the organ. The presence of diffused lymphoid tissue of uterine tube depended on the state of reproductive function of female organism. In the phase of desquamation there was minimal quantity of lymphoid tissue and in the phase of secretion there was maximal quantity of lymphoid tissue

  19. Interactions between the intestinal microbiota and innate lymphoid cells.

    Science.gov (United States)

    Chen, Vincent L; Kasper, Dennis L

    2014-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells.

  20. Innate Lymphoid Cells in Cancer.

    Science.gov (United States)

    Vallentin, Blandine; Barlogis, Vincent; Piperoglou, Christelle; Cypowyj, Sophie; Zucchini, Nicolas; Chéné, Matthieu; Navarro, Florent; Farnarier, Catherine; Vivier, Eric; Vély, Frédéric

    2015-10-01

    The world of lymphocytes has recently expanded. A group of cells, innate lymphoid cells (ILC), has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as IFNγ. Advances in our understanding of NK-cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens without the need for specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples.

  1. IL-12/IL-23p40 Is Highly Expressed in Secondary Lymphoid Organs and the CNS during All Stages of EAE, but Its Deletion Does Not Affect Disease Perpetuation

    Science.gov (United States)

    Cravens, Petra D.; Hussain, Rehana Z.; Miller-Little, William A.; Ben, Li-Hong; Segal, Benjamin M.; Herndon, Emily; Stüve, Olaf

    2016-01-01

    Background Interleukin (IL)-12 and IL-23 are heterodimers that share the p40 subunit, and both cytokines are critical in the differentiation of T helper (Th)1 and Th17 cells, respectively. Th1 and Th17 effector cells have been implicated in the pathogenesis of experimental autoimmune encephalitis (EAE), an animal model of the human central nervous system (CNS) autoimmune demyelinating disorder multiple sclerosis (MS). However, ustekinumab, a monoclonal antibody (mAb) against p40 failed to show efficacy over placebo in a phase II clinical trial in patients with MS. The role of p40 in initial T cell priming and maintenance in secondary lymphoid tissues is not yet well understood. Methods Active EAE was induced in the B6.129-IL12b strain of p40eYFP reporter mice (yet40 mice), and Th1 and Th17 polarized cells were adoptively transferred into p40-deficient mice. Cellular subsets were phenotyped by multi-parameter flow cytometry, and p40 tissue expression was identified by confocal microscopy. Results We show that yet40 mice are susceptible to EAE, and that p40 is highly expressed in secondary lymphoid organs and the CNS during all stages of the disease. Interestingly, p40 expression in the recipient is not required for EAE induction after adoptive transfer of activated and differentiated encephalitogenic Th1 and Th17 cells into p40-deficient mice. Peripheral antagonism of T helper cell trophic factors critical for the differentiation and maintenance of Th1 and Th17 cells ameliorates EAE, indicating that p40 may play a critical role in the induction of CNS autoimmunity but not in its perpetuation. Conclusion Our data may explain why ustekinumab did not ameliorate paraclinical and clinical disease in patients with MS. In patients with already established disease, activated antigen-specific encephalitogenic CD4+ T cells are likely already differentiated, and are not dependent on p40 for maintenance. A clinical trial of longer duration with anti-p40 mAbs or other forms of

  2. Dendritic cell-derived VEGF-A plays a role in inflammatory angiogenesis of human secondary lymphoid organs and is driven by the coordinated activation of multiple transcription factors

    Science.gov (United States)

    Salvi, Valentina; Vermi, William; Gianello, Veronica; Lonardi, Silvia; Gagliostro, Vincenzo; Naldini, Antonella

    2016-01-01

    Lymph node expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Previous work in mice has shown that this process depends on the presence of VEGF-A produced by B cells, macrophages and stromal cells. In humans, however, the cell types and the mechanisms regulating the intranodal production of VEGF-A remain elusive. Here we show that CD11c+ cells represent the main VEGF-A-producing cell population in human reactive secondary lymphoid organs. In addition we find that three transcription factors, namely CREB, HIF-1α and STAT3, regulate the expression of VEGF-A in inflamed DCs. Both HIF-1α and STAT3 are activated by inflammatory agonists. Conversely, CREB phosphorylation represents the critical contribution of endogenous or exogenous PGE2. Taken together, these results propose a crucial role for DCs in lymph node inflammatory angiogenesis and identify novel potential cellular and molecular targets to limit inflammation in chronic diseases and tumors. PMID:27256980

  3. Dendritic cell-derived VEGF-A plays a role in inflammatory angiogenesis of human secondary lymphoid organs and is driven by the coordinated activation of multiple transcription factors.

    Science.gov (United States)

    Salvi, Valentina; Vermi, William; Gianello, Veronica; Lonardi, Silvia; Gagliostro, Vincenzo; Naldini, Antonella; Sozzani, Silvano; Bosisio, Daniela

    2016-06-28

    Lymph node expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Previous work in mice has shown that this process depends on the presence of VEGF-A produced by B cells, macrophages and stromal cells. In humans, however, the cell types and the mechanisms regulating the intranodal production of VEGF-A remain elusive. Here we show that CD11c+ cells represent the main VEGF-A-producing cell population in human reactive secondary lymphoid organs. In addition we find that three transcription factors, namely CREB, HIF-1α and STAT3, regulate the expression of VEGF-A in inflamed DCs. Both HIF-1α and STAT3 are activated by inflammatory agonists. Conversely, CREB phosphorylation represents the critical contribution of endogenous or exogenous PGE2. Taken together, these results propose a crucial role for DCs in lymph node inflammatory angiogenesis and identify novel potential cellular and molecular targets to limit inflammation in chronic diseases and tumors.

  4. Olanzapine-induced hepatopathy in albino rats: A newer model for screening putative hepatoprotective agents, namely silymarin

    Directory of Open Access Journals (Sweden)

    Sengupta Parama

    2010-01-01

    Full Text Available Backgrounds: This study was conducted to establish olanzapine-induced hepatopathy in Wistar albino rats as a newer model to screen putative hepatoprotective agents namely silymarin. Materials and Methods: Albino rats were divided into three groups, namely vehicle control group (CG, olanzapine-treated group (OZ, and olanzapine plus silymarin (OZS treated groups. Both the OZ and OZS groups were treated with the same dose of intraperitoneal olanzapine for 6 weeks and group OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes (SGOT, SGPT, and ALP were measured in all three groups. Results: Histopathological examination of livers of both OZ and OZS groups showed degenerative changes, whereas those of control group showed normal architecture. Liver enzyme levels showed statistically significant rise in comparison to the control group as well as the respective base line values in both the test groups, but the differences in the rise of liver enzymes between the two test groups were not statistically significant. Conclusion: Olanzapine-induced hepatopathy in rats can be used as a model for screening putative hepatoprotective agents and in our setting silymarin has failed to provide any hepatoprotection.

  5. Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells.

    Science.gov (United States)

    Zhang, Zongde; Li, Jianjian; Zheng, Wencheng; Zhao, Guang; Zhang, Hong; Wang, Xiaofei; Guo, Yaqian; Qin, Chuan; Shi, Yan

    2016-02-16

    Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45(+)CD103(+)RALDH(+) cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH(+) cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs.

  6. Stress-induced alterations in the programmed natural cycles of post-natal lymphoid organ development in C57BL/6 mice: Evidence for a regulatory feedback relationship between bone marrow and thymus.

    Science.gov (United States)

    Domínguez-Gerpe, Lourdes

    2007-01-01

    This study investigated some effects of weaning and immobilization stress in C57BL/6 mice aged 22-68 days, i.e., over a period including activation of the hypothalamus-pituitary-adrenal (HPA) axis and puberty. Specifically, the study evaluated the evolution, over the referred age interval, of a set of variables (body, thymus, spleen and axillary lymph nodes weights, the proportion of lymphoid cells in the bone marrow, the relative chemoattraction capacity of thymic supernatants for lymphoid cells and the migratory capacity of bone marrow lymphoid cells) in either weaned mice or weaned mice subjected to immobilization stress, compared to "non-stressed" unweaned mice. Cyclic patterns, observed for most variables in unweaned mice, were especially pronounced in two cases: the relative migratory capacity of bone marrow lymphoid cells collected at different ages towards neonatal thymic supernatant, and the relative chemoattraction capacity of thymic supernatants of different ages as tested against a sample of bone marrow lymphoid cells from mice aged 35 days. Weaning stress tended to intensify the involution stages of the cycles in thymus, spleen and lymph node weight, but increased the relative proportion of lymphoid cells in the bone marrow cell population. Both types of exogenous stress tended to affect cycle phase, i.e., cycle peaks and troughs were shifted in time. Correlations were observed between patterns seen in the thymus and bone marrow, suggesting the existence of an autoregulatory feedback loop governing pre-T cell migration and bone marrow/thymus homeostasis. These results also suggest that exogenous stress acts as a non-programmed regulator, modulating the naturally programmed cyclic patterns.

  7. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain.

    Science.gov (United States)

    Pichery, Mélanie; Mirey, Emilie; Mercier, Pascale; Lefrancais, Emma; Dujardin, Arnaud; Ortega, Nathalie; Girard, Jean-Philippe

    2012-04-01

    IL-33 (previously known as NF from high endothelial venules) is an IL-1 family cytokine that signals through the ST2 receptor and drives cytokine production in mast cells, basophils, eosinophils, invariant NKT and NK cells, Th2 lymphocytes, and type 2 innate immune cells (natural helper cells, nuocytes, and innate helper 2 cells). Little is known about endogenous IL-33; for instance, the cellular sources of IL-33 in mouse tissues have not yet been defined. In this study, we generated an Il-33-LacZ gene trap reporter strain (Il-33(Gt/Gt)) and used this novel tool to analyze expression of endogenous IL-33 in vivo. We found that the Il-33 promoter exhibits constitutive activity in mouse lymphoid organs, epithelial barrier tissues, brain, and embryos. Immunostaining with anti-IL-33 Abs, using Il-33(Gt/Gt) (Il-33-deficient) mice as control, revealed that endogenous IL-33 protein is highly expressed in mouse epithelial barrier tissues, including stratified squamous epithelia from vagina and skin, as well as cuboidal epithelium from lung, stomach, and salivary gland. Constitutive expression of IL-33 was not detected in blood vessels, revealing the existence of species-specific differences between humans and mice. Importantly, IL-33 protein was always localized in the nucleus of producing cells with no evidence for cytoplasmic localization. Finally, strong expression of the Il-33-LacZ reporter was also observed in inflamed tissues, in the liver during LPS-induced endotoxin shock, and in the lung alveoli during papain-induced allergic airway inflammation. Together, our findings support the possibility that IL-33 may function as a nuclear alarmin to alert the innate immune system after injury or infection in epithelial barrier tissues.

  8. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    Science.gov (United States)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  9. [Lymphoid neogenesis and lymphangiogenesis: two newcomers in the pathophysiology of chronic rejection].

    Science.gov (United States)

    Attuil-Audenis, Valérie; Duthey, Aurélie; Patey, Natacha; Gautreau, Chantal; McGregor, Brigitte; Morelon, Emmanuel; Michel, Jean-Baptiste; Nicoletti, Antonino; Thaunat, Olivier

    2009-04-01

    Chronic rejection is one of the main causes of late allograft failure and no therapy is currently available to prevent efficiently its development. Improving the comprehension of the mechanisms involved in the pathophysiology of chronic rejection is a mandatory step to propose innovative therapies that would prolong grafts' survival. Using the rat aortic interposition model of chronic vascular rejection, we have demonstrated that the intragraft inflammatory infiltrate progressively organized itself into a functional ectopic lymphoid tissue (tertiary lymphoid organ) supporting the local synthesis of alloantibody. Thus, during chronic rejection the graft is at the same time the target and the site of elaboration of the humoral allo-immune response. This hypothesis has been confirmed in the clinical setting by the analysis of human grafts (kidneys, hearts and lungs) removed for terminal failure due to chronic rejection. This lymphoid neogenesis process, previously identified in other chronic inflammatory diseases, occurs with a strikingly high frequency in chronically rejected grafts, suggesting that an additional mechanism synergizes to initiate the development of tertiary lymphoid organs during chronic rejection. We propose that the defective lymphatic drainage of chronically rejected organs triggers lymphoid neogenesis and we discuss the complex crosstalk between lymphoid neogenesis and lymphangiogenesis that takes place during chronic rejection.

  10. Lymphoid cells in chicken intestinal epithelium

    DEFF Research Database (Denmark)

    Bjerregaard, P

    1975-01-01

    The intraepithelial lymphoid cells of chicken small intestine were studied by light microscopy using 1 mu Epon sections, and by electron microscopy. Three cell types were found: small lymphocytes, large lymphoid cells, and granular cells. These cells correspond to the theliolymphocytes and globule...

  11. Lymphoid cells in chicken intestinal epithelium

    DEFF Research Database (Denmark)

    Bjerregaard, P

    1975-01-01

    The intraepithelial lymphoid cells of chicken small intestine were studied by light microscopy using 1 mu Epon sections, and by electron microscopy. Three cell types were found: small lymphocytes, large lymphoid cells, and granular cells. These cells correspond to the theliolymphocytes and globule...

  12. B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue

    OpenAIRE

    Lehmann-Horn, Klaus; Wang, Sheng-zhi; Sagan, Sharon A.; Zamvil, Scott S.; von Büdingen, H.-Christian

    2016-01-01

    Ectopic lymphoid tissues (ELT) can be found in multiple sclerosis (MS) and other organ-specific inflammatory conditions. Whether ELT in the meninges of central nervous system (CNS) autoimmune disease exhibit local germinal center (GC) activity remains unknown. In an experimental autoimmune encephalomyelitis model of CNS autoimmunity, we found activation-induced cytidine deaminase, a GC-defining enzyme, in meningeal ELT (mELT) densely populated by B and T cells. To determine GC activity in mEL...

  13. Morphological Features of Lymphoid Structures of Nasooropharynx in Children with Hyperplasia of Pharyngeal Lymphoid Ring

    Directory of Open Access Journals (Sweden)

    L.S. Ovcharenko

    2015-10-01

    Full Text Available The purpose is the features of the immunomorphofunctional organization of the adenoids in children with pharyngeal lymphoid ring hyperplasia were defined. The study included 54 children (random sample from 3 to 7 years examined for the pharyngeal tonsil hypertrophy. Among the 54 selected children, there were 28 (52 % boys and 26 (48 % girls. The cause for surgical removal of the adenoids was the ineffectiveness of conservative therapy. The materials for morphological studies were adenoids of children obtained after adenoidectomy. When analyzing the anamnesis of 54 children with adenoid vegetations aged 3 to 7 years, it was found that among patients with this pathology, those aged 4–6 years predominated. The degree of hypertrophy of the pharyngeal tonsil was the highest among preschool children. Morphometric study of adenoids revealed a reciprocal relationship («scissors» between the relative areas of the follicular and diffuse lymphoid tissue, with a reduction in the length of the zone of lymphoepithelial symbiosis, and an increase in the length of the respiratory epithelium, with preserved local reactive sites.

  14. Lymphoid tissue inducer cells: architects of CD4 immune responses in mice and men.

    Science.gov (United States)

    Kim, M-Y; Kim, K-S; McConnell, F; Lane, P

    2009-07-01

    In this review, we summarize the current understanding of the multiple functions of the mouse lymphoid tissue inducer (LTi) cells in: (i) the development of organized lymphoid tissue, (ii) the generation and maintenance of CD4-dependent immunity in adult lymphoid tissues; and (iii) the regulation of central tolerance in thymus. By contrast with mouse LTi cells, which have been well described, the human equivalent is only just beginning to be characterized. Human LTi-like cells expressing interleukin (IL)-22 have been identified recently and found to differentiate into natural killer (NK) cells. The relationship of LTi cells to NK cells is discussed in the light of several studies reporting a close relationship in the mouse between LTi cells and transcription factor retinoid-related orphan receptor gammat-dependent IL-22 producing NK cells in the gut. We also outline our data suggesting that these cells are present in adult human lymphoid tissues.

  15. Context-Dependent Development of Lymphoid Stroma from Adult CD34+ Adventitial Progenitors

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    Katarzyna M. Sitnik

    2016-03-01

    Full Text Available Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3−PDPN+PDGFRβ+/α+CD34+ stromal adventitial cells in both lymph nodes (LNs and thymus that is located within the vascular niche surrounding PDPN−PDGFRβ+/α−Esam-1+ITGA7+ pericytes. CD34+ adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ re-aggregate grafts, we demonstrate that adult CD34+ adventitial cells are capable of differentiating into multiple lymphoid stroma-like subsets including pericyte-, FRC-, MRC-, and FDC-like cells, the development of which was lymphoid environment-dependent. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34+ adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues.

  16. Innate lymphoid cells involve in tumorigenesis.

    Science.gov (United States)

    Tian, Zhiqiang; van Velkinburgh, Jennifer C; Wu, Yuzhang; Ni, Bing

    2016-01-01

    Innate lymphoid cells (ILCs) promptly initiate cytokine responses to pathogen exposure in the mucosa and mucosal-associated lymphoid tissues. ILCs were recently categorized as being of the lymphoid lineage and have been classified into three groups. ILCs play important roles in immunity against pathogens, and an anti-tumor immune-related function was recently demonstrated. In this review we discuss whether and how ILCs involve in the tumorigenesis, providing new insights into the mechanisms underlying the particular functions of ILCs as well as the potential targets for tumor intervention.

  17. HCV Virus and Lymphoid Neoplasms

    Directory of Open Access Journals (Sweden)

    Yutaka Tsutsumi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

  18. Total lymphoid irradiation and discordant cardiac xenografts

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    Kaplan, E.; Dresdale, A.R.; Diehl, J.T.; Katzen, N.A.; Aronovitz, M.J.; Konstam, M.A.; Payne, D.D.; Cleveland, R.J. (Tufts Univ. School of Medicine, Boston, MA (USA))

    1990-01-01

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

  19. Impaired telomerase activity hinders proliferation and in vitro transformation of Penaeus monodon lymphoid cells.

    Science.gov (United States)

    Jayesh, P; Vrinda, S; Priyaja, P; Philip, Rosamma; Singh, I S Bright

    2016-08-01

    Retaining terminal transferase activity of telomerase, the ribonucleoprotein enzyme which add telomeric repeats on chromosome end is thought to be required to prevent cellular ageing. Additionally, telomerase considered as a marker for cell proliferation and immortalization in eukaryotes. We examined telomerase activity in tissues and lymphoid cell culture of Penaeus monodon. Along with telomerase activity, telomere repeats and an attempt on identification of telomerase reverse transcriptase (PmTERT) were made. Telomeric repeat amplification protocol revealed that telomerase-dependent telomeric lengthening has been taking place in P. monodon and the adult tissues were retaining this capacity throughout their lifespan with the highest activity in ovary, testis and lymphoid organ. However, telomerase activity could not be detected in lymphoid cells in culture. The canonical telomeric repeats added by telomerase of lymphoid tissue extract were identified as TTAGG, but pentameric repeats GGTTA and AGGTT were also added by the telomerase. PmTERT protein sequence (partial) shared 100 % identity with the TERT sequence of Daphnia pulex, 27 % sequence identity with Purple sea urchin and 24-25 % with Zebra fish. Undetectable telomerase activity in lymphoid cell culture supports the hypothesis that the inadequate telomerase activity or gene expression may be a reason that prevents neoplastic transformation and spontaneous immortalization of the cells in vitro. Thus, it is envisaged that telomerase activation in lymphoid cells may surmount cellular ageing for in vitro transformation and cell line establishment.

  20. The biology of innate lymphoid cells.

    Science.gov (United States)

    Artis, David; Spits, Hergen

    2015-01-15

    The innate immune system is composed of a diverse array of evolutionarily ancient haematopoietic cell types, including dendritic cells, monocytes, macrophages and granulocytes. These cell populations collaborate with each other, with the adaptive immune system and with non-haematopoietic cells to promote immunity, inflammation and tissue repair. Innate lymphoid cells are the most recently identified constituents of the innate immune system and have been the focus of intense investigation over the past five years. We summarize the studies that formally identified innate lymphoid cells and highlight their emerging roles in controlling tissue homeostasis in the context of infection, chronic inflammation, metabolic disease and cancer.

  1. Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population.

    Science.gov (United States)

    Lugthart, Gertjan; Melsen, Janine E; Vervat, Carly; van Ostaijen-Ten Dam, Monique M; Corver, Willem E; Roelen, Dave L; van Bergen, Jeroen; van Tol, Maarten J D; Lankester, Arjan C; Schilham, Marco W

    2016-07-01

    Knowledge of human NK cells is based primarily on conventional CD56(bright) and CD56(dim) NK cells from blood. However, most cellular immune interactions occur in lymphoid organs. Based on the coexpression of CD69 and CXCR6, we identified a third major NK cell subset in lymphoid tissues. This population represents 30-60% of NK cells in marrow, spleen, and lymph node but is absent from blood. CD69(+)CXCR6(+) lymphoid tissue NK cells have an intermediate expression of CD56 and high expression of NKp46 and ICAM-1. In contrast to circulating NK cells, they have a bimodal expression of the activating receptor DNAX accessory molecule 1. CD69(+)CXCR6(+) NK cells do not express the early markers c-kit and IL-7Rα, nor killer cell Ig-like receptors or other late-differentiation markers. After cytokine stimulation, CD69(+)CXCR6(+) NK cells produce IFN-γ at levels comparable to CD56(dim) NK cells. They constitutively express perforin but require preactivation to express granzyme B and exert cytotoxicity. After hematopoietic stem cell transplantation, CD69(+)CXCR6(+) lymphoid tissue NK cells do not exhibit the hyperexpansion observed for both conventional NK cell populations. CD69(+)CXCR6(+) NK cells constitute a separate NK cell population with a distinct phenotype and function. The identification of this NK cell population in lymphoid tissues provides tools to further evaluate the cellular interactions and role of NK cells in human immunity.

  2. The role of innate lymphoid cells in healthy and inflamed skin

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte M.; Geisler, Carsten

    2016-01-01

    The skin constitutes the interface between the organism and the environment, and it protects the body from harmful substances in the environment via physical, chemical and immunological barriers. The immunological barrier of the skin comprises both cells from the innate and the adaptive immune...... system. During the last years, it has become clear that innate lymphoid cells play a role in homeostasis and inflammation of the skin in humans and mice. In this review, we will discuss the role of innate lymphoid cells in healthy and inflamed skin with special focus on their role in atopic dermatitis....

  3. Total lymphoid irradiation of intractable rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Herbst, M.; Fritz, H.; Sauer, R.

    1986-12-01

    Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation, (total dose 20 Gy). Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four patients have since died, one of renal failure, another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and reduction in T-helper cells, the number of T-suppressor cells remaining unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored.

  4. The new WHO nomenclature: lymphoid neoplasms.

    Science.gov (United States)

    Leclair, Susan J; Rodak, Bernadette F

    2002-01-01

    The development of the WHO classification of lymphoid neoplasms is a remarkable example of cooperation and communication between pathologists and oncologists from around the world. Joint classification committees of the major hematopathology societies will periodically review and update this classification, facilitating further progress in the understanding and treatment of hematologic malignancies.

  5. The evolution of innate lymphoid cells

    Science.gov (United States)

    Vivier, Eric; van de Pavert, Serge A; Cooper, Max D; Belz, Gabrielle T

    2017-01-01

    Innate lymphoid cells (ILCs) are the most recently discovered group of immune cells. Understanding their biology poses many challenges. We discuss here the current knowledge on the appearance of ILC subsets during evolution and propose how the connection between ILCs and T cells contributes to the robustness of immunity and hence to the fitness of the hosts. PMID:27328009

  6. Conjunctival lymphoma arising from reactive lymphoid hyperplasia

    Directory of Open Access Journals (Sweden)

    Fukuhara Junichi

    2012-09-01

    Full Text Available Abstract Extra nodal marginal zone B-cell lymphoma (EMZL of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU. Specimens from conjunctival tumors in the right eye, oculus dexter (OD, revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS, and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.

  7. Context-Dependent Development of Lymphoid Stroma from Adult CD34+ Adventitial Progenitors

    DEFF Research Database (Denmark)

    Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger;

    2016-01-01

    ) and thymus that is located within the vascular niche surrounding PDPN-PDGFRβ+/α-Esam-1+ITGA7+ pericytes. CD34+ adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ...

  8. Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)-Structure, function and species differences.

    Science.gov (United States)

    Pabst, Reinhard

    2015-08-26

    The advantage of mucosal vaccination in viral and bacterial infections in different age groups is of enormous clinical relevance. The advantages and potential hazards of intranasal vaccination have always to be considered. The intranasal route for vaccination is very successful for some antigens. Specific adjuvants are necessary. In the nose of rodents there is a structured lymphoid tissue (nose-associated lymphoid tissue (NALT)). This abbreviation should not be used for nasopharynx-associated lymphoid tissue, as this includes parts of the tonsils. In children lymphoid tissue is more dispersed in the nose and not concentrated at the bottom of the dorsal nose ducts as in rodents. There are no data on organized lymphoid tissue in the nose of adults. In NALT of rodents there is a unique structure of adhesion molecule expression; the postnatal development and the different composition of T and B lymphocytes in comparison with Peyer's patches document the uniqueness of this lymphoid organ. There is also a mucosa in the nose with antigen-presenting dendritic cells. Thus, it is often unclear whether intranasal vaccination is initiated via NALT or the diffuse nasal mucosa. There are still many open questions e. g., which adjuvant is necessary for a specific virus, bacterium or other allergen, how many doses are critical for an effective nasal vaccination. Species differences are of major importance when extrapolating results from rodents to humans.

  9. Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation.

    Science.gov (United States)

    Pittaluga, S; Bijnens, L; Teodorovic, I; Hagenbeek, A; Meerwaldt, J H; Somers, R; Thomas, J; Noordijk, E M; De Wolf-Peeters, C

    1996-05-15

    In the Working Formulation (WF), non-Hodgkin's lymphomas (NHL) are grouped according to their clinical behavior. These disorders are listed as entities defined by morphology, phenotype, and cytogenetics in the proposed Revised European-American Classification of Lymphoid Neoplasms (REAL), the clinical relevance of which is still debated. We analyzed 670 NHL cases included in two randomized clinical trials (EORTC 20855 WF-intermediate/high-grade and 20856 WF-low-grade malignancy) with histologic material available for review. Based on hematoxylin-eosin-stained sections, 77% of cases could be subtyped. Immunophenotyping was considered to be mandatory only in diagnosing T-cell lymphoma and anaplastic large-cell lymphoma. Of 522 cases subtyped, 11% were mantle cell lymphoma (MCL), 5% were marginal zone B-cell lymphoma (MZBCL), 46% were follicle center lymphoma, and 32% were diffuse large B-cell lymphoma. Statistical analysis and comparisons between classifications were made only within each trial and treatment group. MCL and MZBCL were characterized by a shorter median survival (3.4 and 4.1 years, respectively) in comparison with low- and intermediate-grade WF groups (> 9.3 and 5.8 years, respectively). In terms of progression-free survival, MCL showed a behavior similar to the low-grade group, with frequent relapses. Follicle center cell lymphomas behaved as low-grade lymphomas as defined by the WF and diffuse large B-cell lymphomas as the WF-intermediate grade group. Because several NHL entities have a clinical behavior of their own, their recognition by the REAL classification offers clinicians additional information that is not obtained when the WF is used.

  10. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Joselli S Silva

    Full Text Available Visceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100+ dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT-α, LT-β, CCL19, CCL21, TNF-α, IL-10, IFN-γ and TGF-β, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02 in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100+ dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4 compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P = 0.01. These changes in the spleen were associated with higher frequency of severe disease (7/12 in the animals with disorganized than in animals with organized (2/13, Chi-square, P = 0.01 splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis.

  11. STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE.

    Science.gov (United States)

    Furth, J; Strumia, M

    1931-04-30

    Lymphoid leucemia of the mouse is readily transmitted by intravenous inoculations. The majority of the mice inoculated successfully develop leucemic, a smaller number of them, aleucemic lymphadenosis. The data presented favor the view that leucemic and aleucemic lymphadenosis are essentially the same condition. Leucemia produced by transmission is preceded by an aleucemic stage, in which the lymph nodes and the spleen are uniformly enlarged, and the white blood count and the percentage of lymphocytes are within the normal range but immature lymphocytes are numerous in the circulating blood. Young as well as old mice may develop leucemia if leucotic material enters their circulation. Studies of transmissible leucemia favor the view that leucemia of mammals is a neoplastic disease. The basic problem of leucemia would seem to be determination of the factors that bring about a malignant transformation of lymphoid cells.

  12. Innate lymphoid cells in inflammation and immunity.

    Science.gov (United States)

    McKenzie, Andrew N J; Spits, Hergen; Eberl, Gerard

    2014-09-18

    Innate lymphoid cells (ILCs) were first described as playing important roles in the development of lymphoid tissues and more recently in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. It has now become apparent that ILCs play more complex roles throughout the duration of immune responses, participating in the transition from innate to adaptive immunity and contributing to chronic inflammation. The proximity of ILCs to epithelial surfaces and their constitutive strategic positioning in other tissues throughout the body ensures that, in spite of their rarity, ILCs are able to regulate immune homeostasis effectively. Dysregulation of ILC function might result in chronic pathologies such as allergies, autoimmunity, and inflammation. A new role for ILCs in the maintenance of metabolic homeostasis has started to emerge, underlining their importance in fundamental physiological processes beyond infection and immunity. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Dermatan Sulfate-Free Mice Display Embryological Defects and Are Neonatal Lethal Despite Normal Lymphoid and Non-Lymphoid Organogenesis.

    Directory of Open Access Journals (Sweden)

    Xanthi N Stachtea

    Full Text Available The epimerization of glucuronic acid into iduronic acid adds structural variability to chondroitin/dermatan sulfate polysaccharides. Iduronic acid-containing domains play essential roles in processes such as coagulation, chemokine and morphogen modulation, collagen maturation, and neurite sprouting. Therefore, we generated and characterized, for the first time, mice deficient in dermatan sulfate epimerase 1 and 2, two enzymes uniquely involved in dermatan sulfate biosynthesis. The resulting mice, termed DKO mice, were completely devoid of iduronic acid, and the resulting chondroitin sulfate chains were structurally different from the wild type chains, from which a different protein binding specificity can be expected. As a consequence, a vast majority of the DKO mice died perinatally, with greatly variable phenotypes at birth or late embryological stages such as umbilical hernia, exencephaly and a kinked tail. However, a minority of embryos were histologically unaffected, with apparently normal lung and bone/cartilage features. Interestingly, the binding of the chemokine CXCL13, an important modulator of lymphoid organogenesis, to mouse DKO embryonic fibroblasts was impaired. Nevertheless, the development of the secondary lymphoid organs, including the lymph nodes and spleen, was normal. Altogether, our results indicate an important role of dermatan sulfate in embryological development and perinatal survival.

  14. Characteristic of innate lymphoid cells (ILC

    Directory of Open Access Journals (Sweden)

    Mateusz Adamiak

    2014-12-01

    Full Text Available Innate lymphoid cells (ILC is a newly described family of immune cells that are part of the natural immunity which is important not only during infections caused by microorganisms, but also in the formation of lymphoid tissue, tissue remodeling after damage due to injury and homeostasis tissue stromal cells. Family ILC cells form NK cells (natural killer and lymphoid tissue inducer T cells (LTi, which, although they have different functions, are evolutionarily related. NK cells are producing mainly IFN-γ, whereas LTi cells as NKR+LTi like, IL-17 and/or IL-22, which suggests that the last two cells, can also represent the innate versions of helper T cell - TH17 and TH22. Third population of ILC is formed by cells with characteristics such as NK cells and LTi (ILC22 - which are named NK22 cells, natural cytotoxicity receptor 22 (NCR22 cells or NK receptor-positive (LTi NKR+ LTi cells. Fourth population of ILC cells are ILC17 - producing IL-17, while the fifth is formed by natural helper type 2 T cells (nTH2, nuocyte, innate type 2 helper cells (IH2 and multi-potent progenitor type 2 cells (MPPtype2. Cells of the last population synthesize IL-5 and IL-13. It is assumed that an extraordinary functional diversity of ILC family, resembles T cells, probably because they are under the control of the corresponding transcription factors - as direct regulation factors, such as the family of lymphocytes T.

  15. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Directory of Open Access Journals (Sweden)

    Eoin Neil McNamee

    2016-08-01

    Full Text Available Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues (GALT maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT, which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn’s disease (CD, their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein we discuss the main theories of intestinal tertiary lymphoid tissue neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease.

  16. Therapy of gastric mucosa associated lymphoid tissue lymphoma

    Institute of Scientific and Technical Information of China (English)

    Andrea Morgner; Renate Schmelz; Christian Thiede; Manfred Stolte; Stephan Miehlke

    2007-01-01

    Gastric mucosa associated lymphoid tissue (MALT)lymphoma has recently been incorporated into the World Health Organization (WHO) lymphoma classification,termed as extranodal marginal zone B-cell lymphoma of MALT-type. In about 90% of cases this lymphoma is associated with H pylori infection which has been clearly shown to play a causative role in lymphomagenesis.Although much knowledge has been gained in defining the clinical features, natural history, pathology, and molecular genetics of the disease in the last decade, the optimal treatment approach for gastric MALT lymphomas,especially locally advanced cases, is still evolving. In this review we focus on data for the therapeutic, stage dependent management of gastric MALT lymphoma.Hence, the role of eradication therapy, surgery,chemotherapy and radiotherapy is critically analyzed.Based on these data, we suggest a therapeutic algorithm that might help to better stratify patients for optimal treatment success.

  17. [Immunological profile of lymphoid cells in patients with chronic lymphoid leukemia and immunological complications during the treatment with prednisolone and chlorambucil].

    Science.gov (United States)

    Lohins'kyĭ, V O; Karol', Iu S; Tsiapka, O M; Vyhovs'ka, Ia I

    2009-01-01

    Comparative study of immunological phenotype of lymphoid cells of peripheral blood of patients with chronic lymphoid leukemia (CLL) and immune cytopenia at the treatment with prednisolone and chlorambucil has been carried out. It was shown, that inclusion in the treatment of chlorambucil (chlorambucil + prednisolone) enabled the achievement of remission of immune process at the majority of patients though average duration of remission essentially did not differ. The best clinical result was accompanied by more essential variations of leukemic B-cellular population than during the treatment with prednisolone alone. The reduction of absolute number of lymphocytes in patients with CLL under the treatment with chlorambucil and prednisolone was accompanied by reduction of expression of separate B-cellular antigens of mature cells with minimal signs of their activation. The expediency of a combination of prednisolone with chlorambucil in cases of high leukocytosis and expressed hyperplasia of organs of the limphoid systems.

  18. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency

    Science.gov (United States)

    Maglione, Paul J.; Ko, Huaibin M.; Beasley, Mary B.; Strauchen, James A.; Cunningham-Rundles, Charlotte

    2014-01-01

    Background Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified. Objective We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID. Methods We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH. Results In these subjects regions of PLH contained distinct Band T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings. Conclusion Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell–targeted therapy might disrupt CVID-associated lymphoid hyperplasia. PMID:24131823

  19. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency.

    Science.gov (United States)

    Maglione, Paul J; Ko, Huaibin M; Beasley, Mary B; Strauchen, James A; Cunningham-Rundles, Charlotte

    2014-02-01

    Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified. We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID. We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH. In these subjects regions of PLH contained distinct B- and T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings. Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell-targeted therapy might disrupt CVID-associated lymphoid hyperplasia. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. Effect of seasonal variation on lymphoid tissues of the lizards, Mabuya quinquetaeniata Licht. and Uromastyx aegyptia Forsk.

    Science.gov (United States)

    Hussein, M F; Badir, N; el-Ridi, R; Akef, M

    1978-07-01

    The thymus in the lizards Mabuya quinquetaeniata and Uromastyx aegyptia is highly involuted in winter but exhibits in the other seasons a rich lymphoepithelial organization. The splenic white pulp is severely depleted in winter but is extensively developed in spring, summer and autumn. In these seasons, the splenic lymphoid tissue of Mabuya occurs in a continuous phase throughout the organ obscuring the red pulp, whereas in Uromastyx the white pulp remains localized as periarteriolar aggregates and the red pulp is always clearly delineated. In both lizard species, gut-associated lymphoid tissue is well represented, especially in the large intestines and in Mabuya it is almost similar in different seasons. In Uromastyx, in winter, lymphoid nodules are only found in the caecum and the colon, but during warm seasons, inumerable nodules are distributed throughout the gut. The findings are important for a clearer understanding of immunologic competence in reptiles.

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  9. Isolated lymphoid follicles in colon: Switch points between inflammation and colorectal cancer?

    Institute of Scientific and Technical Information of China (English)

    Ferenc Sipos; Gy(o)rgyi Müzes

    2011-01-01

    Gut-associated lymphoid tissue is supposed to play a central role in both the organization of colonic repair mechanisms and colorectal carcinogenesis. In inflammatory conditions, the number, diameter and density of isolated lymphoid follicles (ILFs) increases. They are not only involved in immune surveillance, but their presence is also indispensable in normal mucosal regeneration of the colon. In carcinogenesis, ILFs may play a dual role.On the one hand they may support tumor growth and the metastatic process by vascular endothelial growth factor receptor signaling and producing a specific cytokine and cellular milieu, but on the other hand their presence is sometimes associated with a better prognosis.The relation of ILFs to bone marrow derived stem cells, follicular dendritic cells, subepithelial myofibroblasts or crypt formation, which are all involved in mucosal repair and carcinogenesis, has not been directly studied. Data about the putative organizer role of ILFs is scattered in scientific literature.

  10. Isolated lymphoid follicles in colon: switch points between inflammation and colorectal cancer?

    Science.gov (United States)

    Sipos, Ferenc; Muzes, Györgyi

    2011-04-07

    Gut-associated lymphoid tissue is supposed to play a central role in both the organization of colonic repair mechanisms and colorectal carcinogenesis. In inflammatory conditions, the number, diameter and density of isolated lymphoid follicles (ILFs) increases. They are not only involved in immune surveillance, but their presence is also indispensable in normal mucosal regeneration of the colon. In carcinogenesis, ILFs may play a dual role. On the one hand they may support tumor growth and the metastatic process by vascular endothelial growth factor receptor signaling and producing a specific cytokine and cellular milieu, but on the other hand their presence is sometimes associated with a better prognosis. The relation of ILFs to bone marrow derived stem cells, follicular dendritic cells, subepithelial myofibroblasts or crypt formation, which are all involved in mucosal repair and carcinogenesis, has not been directly studied. Data about the putative organizer role of ILFs is scattered in scientific literature.

  11. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation. [X-ray

    Energy Technology Data Exchange (ETDEWEB)

    Hoogenhout, J. (St. Radbond Academic Hospital, Nijmegen, Netherlands); Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  12. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.; de Jong, J.; Kal, H.B.; van Munster, P.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  13. Suitability of stratagene reference RNA for analysis of lymphoid tissues

    DEFF Research Database (Denmark)

    Dybkaer, Karen; Zhou, Guimei; Iqbal, Javeed

    2004-01-01

    We evaluated a lymphoid RNA standard prepared in our laboratory for spotted microarrays against the Universal Human Reference standard from Stratagene. Our goal was to determine if the Stratagene standard, which contains only two lymphoid cell lines out of a pool of 10 human cancer cell lines, had...

  14. Suitability of stratagene reference RNA for analysis of lymphoid tissues

    DEFF Research Database (Denmark)

    Dybkaer, Karen; Zhou, Guimei; Iqbal, Javeed;

    2004-01-01

    We evaluated a lymphoid RNA standard prepared in our laboratory for spotted microarrays against the Universal Human Reference standard from Stratagene. Our goal was to determine if the Stratagene standard, which contains only two lymphoid cell lines out of a pool of 10 human cancer cell lines, ha...

  15. A Reproducible Method for Isolation and In Vitro Culture of Functional Human Lymphoid Stromal Cells from Tonsils

    Science.gov (United States)

    Bar-Ephraim, Yotam E.; Konijn, Tanja; Gönültas, Mehmet; Mebius, Reina E.

    2016-01-01

    The stromal compartment of secondary lymphoid organs is classicaly known for providing a mechanical scaffold for the complex interactions between hematopoietic cells during immune activation as well as for providing a niche which is favorable for survival of lymphocytes. In recent years, it became increasingly clear that these cells also play an active role during such a response. Currently, knowledge of the interactions between human lymphoid stroma and hematopoietic cells is still lacking and most insight is based on murine systems. Although methods to isolate stromal cells from tonsils have been reported, data on stability in culture, characterization, and functional properties are lacking. Here, we describe a reproducible and easy method for isolation and in vitro culture of functional human lymphoid stromal cells from palatine tonsils. The cells isolated express markers and characteristics of T cell zone fibroblastic reticular cells (FRCs) and react to inflammatory stimuli by upregulating inflammatory cytokines and chemokines as well as adhesion molecules, as previously described for mouse lymphoid stroma. Also, cultured tonsil stromal cells support survival of human innate lymphoid cells, showing that these stromal cells can function as bone fide FRCs, providing a favorable microenvironment for hematopoietic cells. PMID:27907202

  16. [Reaction of circadian rhythms of the lymphoid system to deep screening from geomagnetic fields of the earth].

    Science.gov (United States)

    Borodin, Iu I; Letiagin, A Y

    1990-02-01

    C57B1/6 inbred mice were placed in hypomagnetic condition during 14 days constantly. Degree of relaxation of geomagnetic field was 10(4). The increase of the number of eosinophil granulocytes was discovered in peripheral blood of mice. Measures of circadian rhythms of blood's absolute lymphocytosis, absolute number of cells in bone marrow, thymus, spleen and inguinal lymph nodes were safe. Adaptation of lymphoid system to hypomagnetic condition was manifested by desynchronization of circadian rhythmicity on the basis of different sensitivity of lymphoid organs, that realized in strengthening of ultradian rhythms with periods of 15 hours. There are indirect data, that show the increase of speed and/or volume of recirculation of lymphoid cells.

  17. Deciphering the Innate Lymphoid Cell Transcriptional Program

    Directory of Open Access Journals (Sweden)

    Cyril Seillet

    2016-10-01

    Full Text Available Innate lymphoid cells (ILCs are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. We used global transcriptional mapping to analyze gene expression in different ILC progenitors. We identified PD-1 to be specifically expressed in PLZF+ ILCp and revealed that the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical. Importantly, induction of ILC lineage commitment required only transient expression of NFIL3 prior to ID2 and TCF-1 expression. These findings highlight the importance of the temporal program that permits commitment of progenitors to the ILC lineage, and they expand our understanding of the core transcriptional program by identifying potential regulators of ILC development.

  18. Innate lymphoid cells and the MHC.

    Science.gov (United States)

    Robinette, M L; Colonna, M

    2016-01-01

    Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible.

  19. Gene Rearrangement Analysis of Orbital Lymphoid Infiltrating Disorders

    Institute of Scientific and Technical Information of China (English)

    Jianhua Yan; Zhongyao Wu; Shuqi Huang; Yongping Li

    2000-01-01

    Purpose: To determine whether the use of polymerase chain reaction for B-cell gene rearrangement in patients with orbital lymphoid infiltrate disorders could be useful in the diagnosis of lymphoma, especially, in differentiating benign lesion from malignant one. Methods: In addition to clinical, pathological, and immunohistochemical evaluations,48 cases of orbital lymphoid infiltrate disorders were examined for immunoglobulin heavy (IgH) gene rearrangement by means of PCR to amplify the FR3 region with formalin-fixed and paraffin-embedded tissues. Results: Gene rearrangement in the third frame-work of the IgH region was detected in specimens obtained from 15 cases of malignant lymphoma, 4 of reactive lymphoid hyperplasia and 3 of orbital pseudotumor. All of these patients showed a discrete band (100bp) which reflected monoclonal proliferation of B lymphocytes. 5 cases of malignant lymphoma, 6 of reactive lymphoid hyperplasia and 15 of orbital pseudotumor did not show a discrete band on PCR. Conclusions: The FR3 region gene rearrangement of Ig heavy in patients with orbital lymphoid infiltrate disorders may be an additional diagnostic tool in differentiating benign from malignant lymphoid diseases and in offering a useful adjunct for diagnosis in difficult or unclear cases. It is a reliable and practical method of gene diagnosis in orbital lymphoid infiltrate disorders and helps to identify the molecular mechanism of malignant lymphoma. Eye Science 2000; 16:15 ~ 21.

  20. Gene Rearrangement Analysis of Orbital Lymphoid Infilktrating Disorders

    Institute of Scientific and Technical Information of China (English)

    JianghuaYan; ZhongyaoWu; 等

    2002-01-01

    Purpose:To determine whether the use of polymerae chain reaction for B-cell gene rearrangement in patients with orbital lymphoid infiltrate disorders could be useful in the diagnosis of lymphoma,especially,in differentiating benign lesion from malignant one.Methoids:In addition to clinical,pathological,and immunohistochemical evaluatons,48 cases of orbital lymphoid infiltrate disorders were examined for immunoglobulin heavy (IgH) gene rearrangement by means of PCR to amplify the FR3 region with formalin-fixed and paraffin-embedded tissues.Results:Gene rearrangement in the third frame-work of the IgH region was detected in specimens obtained from 15 cases of malignant lymphoma,4 of reactive lymphoid hyperplasia and 3 of orbital pseudotumor.All of these patients showed a discrete band (100bp) which reflected monoclonal proliferation of B lymphocytes.5 cases of malignant lymphoma,6 of reactive lymphoid hyperplasia and 15 of orbital pseudotumor did not show a discrete band on PCR.Conclusions:The FR3 region gene rearrangement of Ig heavy in patients with orbital lymphoid infilktrate disorders may be an additional diagnostic tool in differentiating benign from malignant lymphoid diseases and in offering a useful adjunct for diagnosis in difficult or unclear case.It is a reliable and practical method of gene diagnosis in orbital lymphoid infiltrate disorders and helps to identife the molecular mechanism of malignant lymphoma.Eye Science 2000;16:15-21.

  1. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Science.gov (United States)

    McNamee, Eóin N.; Rivera-Nieves, Jesús

    2016-01-01

    Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT), which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn’s disease (CD), their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein, we discuss the main theories of intestinal TLT neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease. PMID:27579025

  2. Developmental changes of lymphoid tissue in Harderian gland of the laying hens

    Directory of Open Access Journals (Sweden)

    Pamela Bejdić

    2014-03-01

    Full Text Available The Harderian gland of 110 laying hens was histologically investigated from the time of hatching to the period of 10 months of age. Tissue sections were stained with haematoxylin and eosin, periodic acid-schiff (PAS and methyl green-pyronin technique. The research shows that lymphoid tissue is colonised by three types of cells: heterophils, lymphocytes and plasma cells. The number of these cells is directly dependent on bird’s age. During the lifetime of the hens there gradually comes a shift in dominance of these three cell types. Lymphoid nodules are detected only in 40-day-old chickens, while later in adult birds Harderian gland is the organ which contain the largest number of mature plasma cells. Some plasma cells contain the Russell bodies with different size and shape.

  3. Back to the drawing board: Understanding the complexity of hepatic innate lymphoid cells.

    Science.gov (United States)

    Marotel, Marie; Hasan, Uzma; Viel, Sébastien; Marçais, Antoine; Walzer, Thierry

    2016-09-01

    Recent studies of immune populations in nonlymphoid organs have highlighted the great diversity of the innate lymphoid system. It has also become apparent that mouse and human innate lymphoid cells (ILCs) have distinct phenotypes and properties. In this issue of the European Journal of Immunology, Harmon et al. [Eur. J. Immunol. 2016. 46: 2111-2120] characterized human hepatic NK-cell subsets. The authors report that hepatic CD56(bright) NK cells resemble mouse liver ILC1s in that they express CXCR6 and have an immature phenotype. However, unlike mouse ILC1s, they express high levels of Eomes and low levels of T-bet, and upon stimulation with tumor cells, secrete low amounts of cytokines. These unexpected findings further support the differences between human and mouse immune populations and prompt the study of the role of hepatic ILC subsets in immune responses.

  4. Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion

    DEFF Research Database (Denmark)

    Nygren, J.M.; Liuba, K.; Breitbach, M.;

    2008-01-01

    and Purkinje neurons. However, through lineage fate-mapping we demonstrate that such in vivo fusion of lymphoid and myeloid blood cells does not occur to an appreciable extent in steady-state adult tissues or during normal development. Rather, fusion of blood cells with different non-haematopoietic cell types...... is induced by organ-specific injuries or whole-body irradiation, which has been used in previous studies to condition recipients of bone marrow transplants. Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion......Recent studies have suggested that regeneration of non-haematopoietic cell lineages can occur through heterotypic cell fusion with haematopoietic cells of the myeloid lineage. Here we show that lymphocytes also form heterotypic-fusion hybrids with cardiomyocytes, skeletal muscle, hepatocytes...

  5. Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

    Science.gov (United States)

    Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E

    2016-06-15

    Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines.

  6. Structural Features of the Lymphoid Tissue of Newborns’ Gastric Mucosa

    OpenAIRE

    Kliuchko, S. S.

    2015-01-01

    72 Wistar rats’ stomachs were examined in order to study the features of the dynamics of the lymphoid cells content and distribution in the newborns rats’ gastric mucosa in normal. Morphometric, histological and statistical methods were used. The most significant changes in the composition of different populations of immune cells of the gastric mucosa lymphoid tissue was found to occur within the first three weeks after birth, when antigen load on the stomach increases in the form of new food...

  7. Cellular and molecular markers in monitoring the fate of lymphoid cell culture from Penaeus monodon Fabricius (1798).

    Science.gov (United States)

    Puthumana, Jayesh; Jose, Seena; Philip, Rosamma; Singh, I S Bright

    2015-12-01

    Lymphoid cell culture from penaeid shrimps has gained much acceptance as an in vitro platform to facilitate research on the development of prophylaxis, and therapeutic strategies against viruses and for cell line development. However, lymphoid cells can be used as platform for in vitro research, only if they are in metabolically and mitotically active state in vitro with unaltered cell surface receptors. Through this study, we addressed the response of lymphoid cells to a new microenvironment at cellular and molecular levels; including the study of mitotic events, DNA synthesis, expression profile of cell cycle genes, cytoskeleton organization, metabolic activity and viral susceptibility. The S-phase entry and synthesis of new DNA was recorded by immunoflourescent technique. Cdc2, CycA, CycB, EF-1α and BUB3 genes involved in cell cycle were studied in both the cells and tissue, of which EF-1α showed an elevated expression in cells in vitro (∼ 19.7%). Cytoskeleton network of the cell was examined by studying the organization of actin filaments. As the markers for metabolic status, mitochondrial dehydrogenase, protein synthesis and glucose assimilation by the cells were also assessed. Viral susceptibility of the cell was determined using WSSV to confirm the preservation of cellular receptors. This study envisages to strengthen the shrimp cell line research and to bring forth lymphoid cell culture system as a 'model' in vitro system for shrimp and crustaceans altogether.

  8. Superficially located enlarged lymphoid follicles characterise nodular gastritis.

    Science.gov (United States)

    Okamura, Takuma; Sakai, Yasuhiro; Hoshino, Hitomi; Iwaya, Yugo; Tanaka, Eiji; Kobayashi, Motohiro

    2015-01-01

    Nodular gastritis is a form of chronic Helicobacter pylori gastritis affecting the gastric antrum and characterised endoscopically by the presence of small nodular lesions resembling gooseflesh. It is generally accepted that hyperplasia of lymphoid follicles histologically characterises nodular gastritis; however, quantitative analysis in support of this hypothesis has not been reported. Our goal was to determine whether nodular gastritis is characterised by lymphoid follicle hyperplasia.The number, size, and location of lymphoid follicles in nodular gastritis were determined and those properties compared to samples of atrophic gastritis. The percentages of high endothelial venule (HEV)-like vessels were also evaluated.The number of lymphoid follicles was comparable between nodular and atrophic gastritis; however, follicle size in nodular gastritis was significantly greater than that seen in atrophic gastritis. Moreover, lymphoid follicles in nodular gastritis were positioned more superficially than were those in atrophic gastritis. The percentage of MECA-79 HEV-like vessels was greater in areas with gooseflesh-like lesions in nodular versus atrophic gastritis.Superficially located hyperplastic lymphoid follicles characterise nodular gastritis, and these follicles correspond to gooseflesh-like nodular lesions observed endoscopically. These observations suggest that MECA-79 HEV-like vessels could play at least a partial role in the pathogenesis of nodular gastritis.

  9. Clinical drawbacks of total lymphoid irradiation: the cons

    Energy Technology Data Exchange (ETDEWEB)

    Myers, L.W.; Ellison, G.W.; Fahey, J.L.; Tesler, A.; Gottlieb, M.S.

    1988-07-01

    Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS.

  10. Generation of multipotent early lymphoid progenitors from human embryonic stem cells.

    Science.gov (United States)

    Larbi, Aniya; Mitjavila-Garcia, Maria Teresa; Flamant, Stéphane; Valogne, Yannick; Clay, Denis; Usunier, Benoît; l'Homme, Bruno; Féraud, Olivier; Casal, Ibrahim; Gobbo, Emilie; Divers, Dominique; Chapel, Alain; Turhan, Ali G; Bennaceur-Griscelli, Annelise; Haddad, Rima

    2014-12-15

    During human embryonic stem cell (ESC) hematopoietic differentiation, the description of the initial steps of lymphopoiesis remains elusive. Using a two-step culture procedure, we identified two original populations of ESC-derived hematopoietic progenitor cells (HPCs) with CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) phenotypes. Bulk cultures and limiting dilution assays, culture with MS5 cells in the presence of Notch ligand Delta-like-1 (DL-1), and ex vivo colonization tests using fetal thymic organ cultures showed that although CD34(+)CD45RA(+)CD7(-) HPCs could generate cells of the three lymphoid lineages, their potential was skewed toward the B cell lineages. In contrast, CD34(+)CD45RA(+)CD7(+) HPCs predominantly exhibited a T/natural killer (NK) cell differentiation potential. Furthermore these cells could differentiate equivalently into cells of the granulo-macrophagic lineage and dendritic cells and lacked erythroid potential. Expression profiling of 18 markers by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs express genes of the lymphoid specification and that CD34(+)CD45RA(+)CD7(-) cells express B-cell-associated genes, while CD34(+)CD45RA(+)CD7(+) HPCs display a T-cell molecular profile. Altogether, these findings indicate that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs correspond to candidate multipotent early lymphoid progenitors polarized toward either the B or T/NK lineage, respectively. This work should improve our understanding of the early steps of lymphopoiesis from pluripotent stem cells and pave the way for the production of lymphocytes for cell-based immunotherapy and lymphoid development studies.

  11. Histopathological study of hepatopathy in four diamondback terrapins(Malaclemys terrapin)%养殖菱斑龟肝病组织病理研究

    Institute of Scientific and Technical Information of China (English)

    雷洁; 王伟喆; 潘连德

    2012-01-01

    Four diagnostically challenging cases of unknown hepatopathy in four female diamondback terrapins(Malaclemys terrapin) are reviewed and important differential diagnoses discussed.The methods are necropsy,blood smear and histopathological section.At necropsy,the livers were dark,atrophied,and the capsule fibrotic.Abnormalities noted in the hemogram are eosinophilia.The number of leukocytes and eosinophils was significantly higher than normal ranges for healthy reptiles.The pathological changes of livers are the most serious and have consistency.Granular degeneration and vacuolar degeneration happened in most hepatic parenchyma cells,and seriously even necrosis.The hepatic veins lined by inflammatory cells and hepatic congestion.At the end,the most hepatic parenchyma cells were necrosis except the portal area.The lesions in eyelids,lung and kidney are mild and not enough to threaten life,and were complications.The lesion in the four terrapins was diagnosed on these results as a hepatopathy,and the terrapins died of liver failure.There is no evidence to prove that is a parasite infection.%研究海口市泓旺农业养殖有限公司特种龟鳖养殖场养殖菱斑龟种龟发病的病例(4个),采用病理解剖和组织切片H.E染色,进行组织病理学研究。病理解剖显示,4只病龟的肝脏为病变最严重器官,出现色深及表面分布白色斑块的病理解剖症状;血涂片显示外周血液中的总白细胞比例及嗜酸性粒细胞比例明显增高;组织切片中可见肝组织病变最严重并具一致性,病龟C、D肝实质细胞普遍出现颗粒变性、以嗜酸性粒细胞为主的肝组织炎性细胞浸润,血铁黄质沉积,病龟B肝静脉扩张、分支血液回流受阻,肝窦间隙扩张淤血,部分肝细胞转化为空泡变性,病龟A肝实质细胞坏死、肝细胞索消失。4只病龟肝脏表面还出现局部纤维化坏死,眼睑组织静脉周围也出现嗜酸性粒细胞为主的炎性细胞浸润。根

  12. Total lymphoid irradiation for multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.

  13. Close Encounters of Lymphoid Cells and Bacteria

    Science.gov (United States)

    Cruz-Adalia, Aranzazu; Veiga, Esteban

    2016-01-01

    During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases. Some innate immune cells, usually named antigen-presenting cells, such as macrophages or dendritic cells, are able to process internalized invaders and present their antigens to lymphocytes, triggering the adaptive immune response. Nevertheless, the traditional boundary of separated roles between innate and adaptive immunity has been blurred by several studies, showing that very specialized populations of lymphocytes (cells of the adaptive immunity) behave similarly to cells of the innate immunity. These “innate-like” lymphocytes include γδ T cells, invariant NKT cells, B-1 cells, mucosal-associated invariant T cells, marginal zone B cells, and innate response activator cells, and together with the newly described innate lymphoid cells are able to rapidly respond to bacterial infections. Strikingly, our recent data suggest that conventional CD4+ T cells, the paradigm of cells of the adaptive immunity, also present innate-like behavior, capturing bacteria in a process called transinfection. Transinfected CD4+ T cells digest internalized bacteria like professional phagocytes and secrete large amounts of proinflammatory cytokines, protecting for further bacterial challenges. In the present review, we will focus on the data showing such innate-like behavior of lymphocytes following bacteria encounter.

  14. Transcriptional profiling of peripheral lymphoid tissue reveals genes and networks linked to SSBP/1 scrapie pathology in sheep.

    Science.gov (United States)

    Gossner, Anton; Roupaka, Sofia; Foster, Jim; Hunter, Nora; Hopkins, John

    2011-12-15

    Transmissible spongiform encephalopathies (TSEs) are slow and progressive neurodegenerative diseases of humans and animals. The major target organ for all TSEs is the brain but some TSE agents are associated with prior accumulation within the peripheral lymphoid system. Many studies have examined the effects of scrapie infection on the expression of central nervous system (CNS) genes, but this study examines the progression of scrapie pathology in the peripheral lymphoid system and how scrapie infection affects the transcriptome of the lymph nodes and spleen. Infection of sheep with SSBP/1 scrapie resulted in PrP(Sc) deposition in the draining prescapular lymph node (PSLN) by 25 days post infection (dpi) in VRQ/VRQ genotype sheep and 75 dpi in tonsils and spleen. Progression of PrP(Sc) deposition in VRQ/ARR animals was 25 dpi later in the PSLN and 250 dpi later in spleen. Microarray analysis of 75 dpi tissues from VRQ/VRQ sheep identified 52 genes in PSLN and 37 genes in spleen cells that showed significant difference (P ≤ 0.05) between scrapie-infected and mock-infected animals. Transcriptional pathway analysis highlighted immunological disease, cell death and neurological disease as the biological pathways associated with scrapie pathogenesis in the peripheral lymphoid system. PrP(Sc) accumulation of lymphoid tissue resulted in the repression of genes linked to inflammation and oxidative stress, and the up-regulation of genes related to apoptosis.

  15. Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor

    Science.gov (United States)

    Kuzin, Igor; Sun, Hongliang; Moshkani, Safiekhatoon; Feng, Changyong; Mantalaris, Athanasios; Wu, JH David; Bottaro, Andrea

    2011-01-01

    Peripheral lymphoid organs (PLOs), the primary sites of development of adaptive immune responses, display a complex structural organization reflecting separation of cellular subsets (e.g. T and B lymphocytes) and functional compartments which is critical for immune function. The generation of in vitro culture systems capable of recapitulating salient features of PLOs for experimental, biotechnological and clinical applications would be highly desirable, but has been hampered so far by the complexity of these systems. We have previously developed a three-dimensional bioreactor system for long-term, functional culture of human bone marrow cells on macroporous microspheres in a packed-bed bioreactor with frequent medium change. Here we adapt the same system for culture of human primary cells from PLOs (tonsil) in the absence of specific exogenous growth factors or activators. Cells in this system displayed higher viability over several weeks, and maintain population diversity and cell surface markers largely comparable to primary cells. Light microscopy showed cells organizing in large diverse clusters within the scaffold pores and presence of B cell-enriched areas. Strikingly, these cultures generated a significant number of antibody-producing B cells when challenged with a panel of diverse antigens, as expected from a lymphoid tissue. Thus the three-dimensional tonsil bioreactor culture system may serve as a useful model of PLOs by recapitulating their structural organization and function ex vivo. PMID:21309085

  16. Alloantigens of human lymphoid cell lines; `human Ia-like antigens'

    Science.gov (United States)

    Koyama, K.; Nakamuro, K.; Tanigaki, N.; Pressman, D.

    1977-01-01

    Membrane glycoproteins that appear to belong to a new alloantigen system were partially purified by gel filtration and lentil-lectin affinity chromatography from a non-ionic detergent (Renex 30) solubilized membrane fraction of each of two Burkitt lymphoma cell lines, B46M and Daudi. The preparations were radioiodinated and further purified by gel filtration, lentil—lectin affinity chromatography and anti-HLA antibody affinity chromatography. The labelled preparations thus obtained did not have binding activity with any of rabbit anti-HLA, rabbit anti-human β2-microglobulin and rabbit anti-human IgG-Fab antisera, but did have a high level of binding activity with rabbit anti-B-cell membrane antiserum. Moreover, the labelled preparations showed relatively high binding activity with some conventional HLA typing sera. Out of sixty-eight human tissue typing alloantisera tested, three (Berlin 373, Betz and TO-29-01) gave especially high binding with both of the labeled preparations. The antigens involved in reaction with these alloantisera and also with the rabbit anti-B-cell membrane antiserum contained two components, one 31,000 ∼ 32,000 daltons and another 24,000 ∼ 25,000 daltons, bound non-covalently. The alloantigens were specific to B cell type cell lines (B-lymphoid cell lines and Burkitt-lymphoma cell lines) in cultured cell lines and also to B lymphocytes in peripheral blood. In organs and tissues, however, they were found to be present widely distributed in lymphoid organs (thymus as well as spleen and lymph node) and in non-lymphoid organs (including liver, kidney, testis and heart). PMID:24587

  17. Inhibition of autophagy overcomes glucocorticoid resistance in lymphoid malignant cells.

    Science.gov (United States)

    Jiang, Lei; Xu, Lingzhi; Xie, Jiajun; Li, Sisi; Guan, Yanchun; Zhang, Yan; Hou, Zhijie; Guo, Tao; Shu, Xin; Wang, Chang; Fan, Wenjun; Si, Yang; Yang, Ya; Kang, Zhijie; Fang, Meiyun; Liu, Quentin

    2015-01-01

    Glucocorticoid (GC) resistance remains a major obstacle to successful treatment of lymphoid malignancies. Till now, the precise mechanism of GC resistance remains unclear. In the present study, dexamethasone (Dex) inhibited cell proliferation, arrested cell cycle in G0/G1-phase, and induced apoptosis in Dex-sensitive acute lymphoblastic leukemia cells. However, Dex failed to cause cell death in Dex-resistant lymphoid malignant cells. Intriguingly, we found that autophagy was induced by Dex in resistant cells, as indicated by autophagosomes formation, LC3-I to LC3-II conversion, p62 degradation, and formation of acidic autophagic vacuoles. Moreover, the results showed that Dex reduced the activity of mTOR pathway, as determined by decreased phosphorylation levels of mTOR, Akt, P70S6K and 4E-BP1 in resistant cells. Inhibition of autophagy by either chloroquine (CQ) or 3-methyladenine (3-MA) overcame Dex-resistance in lymphoid malignant cells by increasing apoptotic cell death in vitro. Consistently, inhibition of autophagy by stably knockdown of Beclin1 sensitized Dex-resistant lymphoid malignant cells to induction of apoptosis in vivo. Thus, inhibition of autophagy has the potential to improve lymphoid malignancy treatment by overcoming GC resistance.

  18. [Clonality lymphoid study through rearrangement analysis of antigen receptor].

    Science.gov (United States)

    Villamizar-Rivera, Nicolás; Olaya, Natalia

    2015-01-01

    As a rule, malignant lymphoid proliferations are clonal. While most of the time the biological potential can be established through routine pathologic examination and auxiliary techniques, some cases are difficult to classify. Moreover, there are situations in which there are dominant clones whose analysis are important, such as occur in autoimmune diseases and immunodeficiency. This paper presents in an understandable way the main techniques for the study of clonality in lymphoid lesions, i.e. the analysis of rearrangements of antigen receptor genes by multiplex polymerase chain reaction (PCR) based tests.

  19. Distribution in law of the dialectical type of TCM of chronic hepatopathy%慢性肝病中医证候规律分布特征

    Institute of Scientific and Technical Information of China (English)

    侯岩; 崔丽萍; 张明香; 颜迎春

    2012-01-01

    Objective To investigate the law of dialectical type of TCM of chronic hepatopathy and predicting treatment results. Methods A retrospective survey was made on 1025 cases of chronic hepatitis and liver cirrhosis from September 2008 to January 2011. Results From high to low frequency order of Chinese medicinal symptom is burnout>irascibility>anxiety>loss of vitality> dry mouth> fatigue> sighing. From high to low frequency order of dialectical typing of TCM is liver-stagnation and spleen-deficiency>liver qi stagnation>damp -heat in the liver and the gall>obstruction of collaterals by blood stasis incoordination between liver and stomach>Yang deficiency of spleen and kidney, insufficiency of liver and kidney>Qi and Damp Stagnation. Conclusion liver-stagnation and spleen-deficiency runs through the disease course, dysfunction of Qi, deficiency of healthy Qi are the key points of disease development course.%目的 探讨慢性肝病的中医症候及中医证型分布特点与疾病预后的关系.方法 对2008年9月至2011年1月各种慢性肝炎、肝硬化患者1025例进行回顾性调查.结果 慢性肝病患者中出现症候频率较高的依次为倦怠、急躁易怒、烦躁、神疲、口干、困重、太息.证型分布依次为肝郁脾虚>肝气郁结>肝胆湿热>血瘀阻络>肝胃不和>脾肾阳虚>肝肾不足>气滞湿阻>寒湿.结论肝郁脾虚贯穿于慢性肝病的整个病程中,气机的不畅、正气的不足是肝病进展的关键.

  20. Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage.

    Science.gov (United States)

    Ishizuka, Isabel E; Chea, Sylvestre; Gudjonson, Herman; Constantinides, Michael G; Dinner, Aaron R; Bendelac, Albert; Golub, Rachel

    2016-03-01

    The precise lineage relationship between innate lymphoid cells (ILCs) and lymphoid tissue-inducer (LTi) cells is poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and found that its bifurcation was marked by differential induction of the transcription factors PLZF and TCF1. Acquisition of individual effector programs specific to the ILC subsets ILC1, ILC2 and ILC3 was initiated later, at the common ILC precursor stage, by transient expression of mixed ILC1, ILC2 and ILC3 transcriptional patterns, whereas, in contrast, the development of LTi cells did not go through multilineage priming. Our findings provide insight into the divergent mechanisms of the differentiation of the ILC lineage and LTi cell lineage and establish a high-resolution 'blueprint' of their development.

  1. The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.

    Science.gov (United States)

    Seehus, Corey R; Aliahmad, Parinaz; de la Torre, Brian; Iliev, Iliyan D; Spurka, Lindsay; Funari, Vincent A; Kaye, Jonathan

    2015-06-01

    Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.

  2. File list: InP.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

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  8. File list: His.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: ALL.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. Functional differences between human NKp44- and NKp44+ RORC+ innate lymphoid cells

    NARCIS (Netherlands)

    K. Hoorweg (Kerim); C.P. Peters (Charlotte); F.H.J. Cornelissen (Ferry); P. Aparicio-Domingo (Patricia); N. Papazian (Natalie); G. Kazemier (Geert); J.M. Mjösberg (Jenny); H. Spits (Hergen); T. Cupedo (Tom)

    2012-01-01

    textabstractHuman RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines

  11. Functional differences between human NKp44- and NKp44+ RORC+ innate lymphoid cells

    NARCIS (Netherlands)

    K. Hoorweg (Kerim); C.P. Peters (Charlotte); F.H.J. Cornelissen (Ferry); P. Aparicio-Domingo (Patricia); N. Papazian (Natalie); G. Kazemier (Geert); J.M. Mjösberg (Jenny); H. Spits (Hergen); T. Cupedo (Tom)

    2012-01-01

    textabstractHuman RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines

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    Lifescience Database Archive (English)

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  13. File list: InP.Bld.05.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

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  1. File list: NoD.Bld.20.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

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  4. File list: Oth.Bld.20.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

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  5. File list: InP.Bld.20.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

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  6. File list: NoD.Bld.05.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

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  7. File list: His.Bld.20.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

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  8. Conjunctiva-associated lymphoid tissue in avian mucosal immunity

    NARCIS (Netherlands)

    Ginkel, van F.W.; Gulley, S.L.; Lammers, A.; Hoerr, F.J.; Gurjar, R.; Toro, H.

    2012-01-01

    Conjunctiva-associated lymphoid tissue’s (CALT) role in generating avian mucosal adaptive immunity was measured by analyzing cellular composition, expression of the polymeric immunoglobulin receptor (pIgR), and production of cytokines and antibodies in chickens ocular exposed to a replication-defici

  9. Occurrence of lymphoid cells in the intestine of the Goldfish

    NARCIS (Netherlands)

    Weinberg, Steven

    1975-01-01

    The Goldfish intestine normally contains a large number of lymphocytes, many of them being present in the epithelial layer. After stimulation with antigen, the number of lymphoid cells does not increase, but the proportion of large pyroninophilic cells and plasma cells does. It seems therefore that

  10. Quantitative image analysis of HIV-1 infection in lymphoid tissue

    Energy Technology Data Exchange (ETDEWEB)

    Haase, A.T.; Zupancic, M.; Cavert, W. [Univ. of Minnesota Medical School, Minneapolis, MN (United States)] [and others

    1996-11-08

    Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally design and monitor therapy. A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productivity infected cells. Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment. 22 refs., 2 figs., 2 tabs.

  11. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  12. 9 CFR 113.31 - Detection of avian lymphoid leukosis.

    Science.gov (United States)

    2010-01-01

    ..., shall be done in chick embryo cell cultures. (1) Each vaccine virus, cytopathic to chick embryo... lymphoid leukosis virus can be propagated on cell culture during the 21-day growth period. If a vaccine... preparation of such questionable vaccine. (2) When cell cultures are tested, 5 ml of the final cell suspension...

  13. Misdiagnoses Analysis of 20 Cases of Spontaneous Bacterial Peritonitis (SBP) Complicated with Chronic Hepatopathy%慢性肝病合并自发性细菌性腹膜炎20例误诊分析

    Institute of Scientific and Technical Information of China (English)

    魏兆勇; 张分明; 李松柏; 褚廷广; 张振洪

    2011-01-01

    目的 探讨慢性肝病合并自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)早期临床特点,以提高诊治水平.方法 回顾性分析我院2008年10月~2009年12月收治的慢性肝病合并SBP早期误诊20例的临床资料.结果 本组早期误诊为急性胃肠炎7例,胆道感染4例,上呼吸道感染、门静脉血栓、腹腔肿瘤、肝肾综合征各2例,结核性腹膜炎1例,后根据临床表现、医技检查确诊为典型SBP.结论 慢性肝病合并SBP早期临床表现不典型,体征欠缺,腹腔积液白细胞数未达到诊断标准,首次误诊以急性胃肠炎、胆道感染最多.提示临床医师在诊治过程中一定要重视临床表现的演变,勿过分依赖医技检查结果,以减少误诊.%Objective To explore the early manifestations of spontaneous bacterial peritonitis (SBP) complicated with chronic hepatopathy and to improve diagnosis and treatment level.Methods We reviewed the clinical data of 20 eases SBP complicated with chronic hepatopathy, misdiagnosed during October 2008 and December 2009 in our hospital.Results 7 cases were first misdiagnosed as acute gastroenteritis; 4 eases as infection of biliary tract; 2 eases as upper respiratory tract infection, pylethrombosis, abdominal cavity tumor, hepatorenal syndrome, respectively; 1 ease as tuberculous peritonitis.They were confirmed as SBP by clinical manifestations and medical technology examinations in the end.Conclusion It is an atypical manifestation of SBP complicated with chronic hepatopathy in the early period.They are rare of signs, and not enough WBC in ascites.Misdiagnoses tend to be cute gastroenteritis and infection of biliary tract.Clinicians are reminded to take clinical development seriously in diagnosing and treating process, instead of rely too much on the results of medical technology.

  14. Issues in diagnosis of small B cell lymphoid neoplasms involving the bone marrow and peripheral blood. Report on the Bone Marrow Workshop of the XVIIth meeting of the European Association for Haematopathology and the Society for Hematopathology.

    Science.gov (United States)

    Porwit, Anna; Fend, Falko; Kremer, Marcus; Orazi, Attilio; Safali, Mükerrem; van der Walt, Jon

    2016-09-01

    Small B cell lymphoid neoplasms are the most common lymphoproliferative disorders involving peripheral blood (PB) and bone marrow (BM). The Bone Marrow Workshop (BMW) organized by the European Bone Marrow Working Group (EBMWG) of the European Association for Haematopathology (EAHP) during the XVIIth EAHP Meeting in Istanbul, October 2014, was dedicated to discussion of cases illustrating how the recent advances in immunophenotyping, molecular techniques and cytogenetics provide better understanding and classification of these entities. Submitted cases were grouped into following categories: (i) cases illustrating diagnostic difficulties in chronic lymphocytic leukaemia (CLL); (ii) cases of BM manifestations of small B cell lymphoid neoplasms other than CLL; (iii) transformation of small B cell lymphoid neoplasms in the BM; and (iv) multiclonality and composite lymphomas in the BM. This report summarizes presented cases and conclusions of the BMW and provides practical recommendations for classification of the BM manifestations of small B cell lymphoid neoplasms based on the current state of knowledge.

  15. Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis.

    Science.gov (United States)

    Mohapatra, A; Van Dyken, S J; Schneider, C; Nussbaum, J C; Liang, H-E; Locksley, R M

    2016-01-01

    Group 2 innate lymphoid cells (ILC2s) have an important role in acute allergic lung inflammation. Given their distribution and function, lung ILC2s are hypothesized to coordinate epithelial responses to the external environment; however, how barrier surveillance is linked to ILC2 activation remains unclear. Here, we demonstrate that alveolar type II cells are the main source of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) generated in response to chitin or migratory helminths. IL-33 and TSLP synergistically induce an interferon regulatory factor 4 (IRF4)-IL-9 program in ILC2s, and autocrine IL-9 promotes rapid IL-5 and IL-13 production required for optimal epithelial responses in the conducting airways. Thus, ILC2s link alveolar function to regulation of airway flow, revealing a key interaction between resident lymphoid and structural cells that might underlie similar organizational hierarchies in other organs.

  16. Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease.

    Science.gov (United States)

    Randolph, Gwendalyn J; Bala, Shashi; Rahier, Jean-François; Johnson, Michael W; Wang, Peter L; Nalbantoglu, ILKe; Dubuquoy, Laurent; Chau, Amélie; Pariente, Benjamin; Kartheuser, Alex; Zinselmeyer, Bernd H; Colombel, Jean-Frederic

    2016-12-01

    Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell-rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Noorjahan Banu Alitheen

    Full Text Available The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+, a majority of those emigrating onto the supporting membrane were Bu-1a(- and IgM(+. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240 was examined.

  18. Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell depletion.

    Science.gov (United States)

    Zhang, Zheng; Cheng, Liang; Zhao, Juanjuan; Li, Guangming; Zhang, Liguo; Chen, Weiwei; Nie, Weiming; Reszka-Blanco, Natalia J; Wang, Fu-Sheng; Su, Lishan

    2015-09-01

    Group 3 innate lymphoid cells (ILC3s) have demonstrated roles in promoting antibacterial immunity, maintaining epithelial barrier function, and supporting tissue repair. ILC3 alterations are associated with chronic inflammation and inflammatory disease; however, the characteristics and relevant regulatory mechanisms of this cell population in HIV-1 infection are poorly understood due in part to a lack of a robust model. Here, we determined that functional human ILC3s develop in lymphoid organs of humanized mice and that persistent HIV-1 infection in this model depletes ILC3s, as observed in chronic HIV-1-infected patients. In HIV-1-infected mice, effective antiretroviral therapy reversed the loss of ILC3s. HIV-1-dependent reduction of ILC3s required plasmacytoid dendritic cells (pDCs), IFN-I, and the CD95/FasL pathway, as targeted depletion or blockade of these prevented HIV-1-induced ILC3 depletion in vivo and in vitro, respectively. Finally, we determined that HIV-1 infection induces CD95 expression on ILC3s via a pDC- and IFN-I-dependent mechanism that sensitizes ILC3s to undergo CD95/FasL-mediated apoptosis. We conclude that chronic HIV-1 infection depletes ILC3s through pDC activation, induction of IFN-I, and CD95-mediated apoptosis.

  19. Inhibition of nuclear factor kappa B activation reduces Coxsackievirus B3 replication in lymphoid cells.

    Science.gov (United States)

    Sobotta, Katharina; Wilsky, Steffi; Althof, Nadine; Wiesener, Nadine; Wutzler, Peter; Henke, Andreas

    2012-02-01

    Interactions between viral replication machineries and host cell metabolism display interesting information how certain viruses capitalize cellular pathways to support progeny production. Among those pathogens, Coxsackievirus B3 (CVB3) has been identified to manipulate intracellular signaling very comprehensively. Next to others, this human pathogenic virus causes acute and chronic forms of myocarditis, pancreatitis, and meningitis. Here, activation of nuclear factor kappa B (NFκB) signaling appears to be involved in successful infection. Viral replication is not restricted to solid organs but involves susceptible immune cells as well. In the present study, p65 phosphorylation as one aspect of NFκB activation and inhibition via BAY 11-7085 administration was analyzed in the context of CVB3 replication in lymphoid cells. During CVB3 infection, an up-regulation of p65 translation is detectable, which is accompanied by noticeable phosphorylation. Inhibition of NFκB signaling reduces viral replication in a dose- and time-dependent manner. Taken together, these results indicate that during CVB3 replication in human and murine lymphoid cells, NFκB signaling is activated and facilitates viral replication. Therefore, antiviral strategies to target such central cellular signaling pathways may represent potential possibilities for the development of new virostatica. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts.

    Science.gov (United States)

    Hautz, Theresa; Zelger, Bettina G; Nasr, Isam W; Mundinger, Gerhard S; Barth, Rolf N; Rodriguez, Eduardo D; Brandacher, Gerald; Weissenbacher, Annemarie; Zelger, Bernhard; Cavadas, Pedro; Margreiter, Raimund; Lee, W P Andrew; Pratschke, Johann; Lakkis, Fadi G; Schneeberger, Stefan

    2014-09-01

    The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T- and B-cell infiltration.

  1. Hepatic nodular lymphoid lesion with increased IgG4-positive plasma cells associated with primary biliary cirrhosis: a report of two cases.

    Science.gov (United States)

    Calvo, Jessica; Carbonell, Nicolas; Scatton, Olivier; Marzac, Christophe; Ganne-Carrie, Nathalie; Wendum, Dominique

    2015-11-01

    The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as « probable histological feature of IgG4-related disease ». There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified.

  2. Regulation of intestinal health and disease by innate lymphoid cells.

    Science.gov (United States)

    Sonnenberg, Gregory F

    2014-09-01

    Innate lymphoid cells (ILCs) are a recently appreciated immune cell population that is constitutively found in the healthy mammalian gastrointestinal (GI) tract and associated lymphoid tissues. Translational studies have revealed that alterations in ILC populations are associated with GI disease in patients, such as inflammatory bowel disease, HIV infection and colon cancer, suggesting a potential role for ILCs in either maintaining intestinal health or promoting intestinal disease. Mouse models identified that ILCs have context-dependent protective and pathologic functions either during the steady state, or following infection, inflammation or tissue damage. This review will discuss the associations of altered intestinal ILCs with human GI diseases, and the functional consequences of targeting ILCs in mouse models. Collectively, our current understanding of ILCs suggests that the development of novel therapeutic strategies to modulate ILC responses will be of significant clinical value to prevent or treat human GI diseases.

  3. [TINU syndrome and lymphoid interstitial alveolitis: a new observation].

    Science.gov (United States)

    Khammassi, Naziha; Mohsen, Dorsaf; Ounissi, Mondher; Tougourti, Mohamed Nejib; Hamza, Mohsen

    2011-02-01

    TINU syndrome is a rare entity known Dobrin disease, combining uveitis mostly bilateral and recurrent with acute tubulo interstitial nephritis (AIN) occurring in young adults. The etiology and pathogenesis of this syndrome remain unknown. To report a new case of TINU syndrome and to discuss its etiopathogenesis. This 33 year old women is hospitalized for exploration of acute renal failure, in a context of deterioration of general condition, associated with a unilateral anterior uveitis. The bronchoalveolar lavage showed lymphoid interstitial alveolitis with CD4 and the renal biopsy found lesions characteristic of AIN. Evolution under corticoïd treatment was favorable. Lymphoid interstitial alveolitis associated with TINU syndrome has been reported only twice before. The discovery of a TINU syndrome must practice bronchoalveolar lavage in search of sub clinical pulmonary involvement.

  4. Treatment of intractable rheumatoid arthritis with lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Strober, S.; Kotzin, B.L.; Hoppe, R.T.; Slavin, S.; Gottlieb, M.; Calin, A.; Fuks, Z.; Kaplan, H.S.

    1981-01-01

    Subdiaphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdiaphragmatic lymphoid tissues in fractionated doses of 150 to 250 rad each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.

  5. Total lymphoid irradiation in refractory systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.

    1986-07-01

    In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

  6. Lymphoid proliferations in the orbit: malignant or benign?

    OpenAIRE

    van der Gaag, R.; Koornneef, L.; Heerde, P. van; Vroom, T M; Pegels, J H; Feltkamp, C.A.; Peeters, H J; Gillissen, J P; Bleeker, G M; Feltkamp, T E

    1984-01-01

    Clinical, pathological, and immunological analysis of 20 patients with ocular adnexal lymphoid disease has demonstrated several parameters which are useful for distinguishing malignant from benign lesions. Patients in the fourth or fifth decade of life presenting with an acute history of pain, oedema, epiphora, double vision, and ptosis, with a mass localised in the lacrimal gland area, are more likely to have a pseudolymphoma or a chronic inflammatory lesion than a true non-Hodgkin lymphoma ...

  7. Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection.

    Science.gov (United States)

    Gillespie, Alyssa Lundgren; Teoh, Jeffrey; Lee, Heather; Prince, Jessica; Stadnisky, Michael D; Anderson, Monique; Nash, William; Rival, Claudia; Wei, Hairong; Gamache, Awndre; Farber, Charles R; Tung, Kenneth; Brown, Michael G

    2016-02-01

    The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust D(k)-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen.

  8. Human natural killer cell development in secondary lymphoid tissues.

    Science.gov (United States)

    Freud, Aharon G; Yu, Jianhua; Caligiuri, Michael A

    2014-04-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34(+)CD45RA(+) hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Treatment of intractable lupus nephritis with total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-04-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

  10. Approach to cutaneous lymphoid infiltrates: When to consider lymphoma?

    Directory of Open Access Journals (Sweden)

    Yann Vincent Charli-Joseph

    2016-01-01

    Full Text Available Cutaneous lymphoid infiltrates (CLIs are common in routine dermatopathology. However, differentiating a reactive CLI from a malignant lymphocytic infiltrate is often a significant challenge since many inflammatory dermatoses can clinically and/or histopathologically mimic cutaneous lymphomas, coined pseudolymphomas. We conducted a literature review from 1966 to July 1, 2015, at PubMed.gov using the search terms: Cutaneous lymphoma, cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia, simulants/mimics/imitators of cutaneous lymphomas, and cutaneous lymphoid infiltrates. The diagnostic approach to CLIs and the most common differential imitators of lymphoma is discussed herein based on six predominant morphologic and immunophenotypic, histopathologic patterns: (1 Superficial dermal T-cell infiltrates (2 superficial and deep dermal perivascular and/or nodular natural killer/T-cell infiltrates (3 pan-dermal diffuse T-cell infiltrates (4 panniculitic T-cell infiltrates (5 small cell predominant B-cell infiltrates, and (6 large-cell predominant B-cell infiltrates. Since no single histopathological feature is sufficient to discern between a benign and a malignant CLI, the overall balance of clinical, histopathological, immunophenotypic, and molecular features should be considered carefully to establish a diagnosis. Despite advances in ancillary studies such as immunohistochemistry and molecular clonality, these studies often display specificity and sensitivity limitations. Therefore, proper clinicopathological correlation still remains the gold standard for the precise diagnosis of CLIs.

  11. Approach to Cutaneous Lymphoid Infiltrates: When to Consider Lymphoma?

    Science.gov (United States)

    Charli-Joseph, Yann Vincent; Gatica-Torres, Michelle; Pincus, Laura Beth

    2016-01-01

    Cutaneous lymphoid infiltrates (CLIs) are common in routine dermatopathology. However, differentiating a reactive CLI from a malignant lymphocytic infiltrate is often a significant challenge since many inflammatory dermatoses can clinically and/or histopathologically mimic cutaneous lymphomas, coined pseudolymphomas. We conducted a literature review from 1966 to July 1, 2015, at PubMed.gov using the search terms: Cutaneous lymphoma, cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia, simulants/mimics/imitators of cutaneous lymphomas, and cutaneous lymphoid infiltrates. The diagnostic approach to CLIs and the most common differential imitators of lymphoma is discussed herein based on six predominant morphologic and immunophenotypic, histopathologic patterns: (1) Superficial dermal T-cell infiltrates (2) superficial and deep dermal perivascular and/or nodular natural killer/T-cell infiltrates (3) pan-dermal diffuse T-cell infiltrates (4) panniculitic T-cell infiltrates (5) small cell predominant B-cell infiltrates, and (6) large-cell predominant B-cell infiltrates. Since no single histopathological feature is sufficient to discern between a benign and a malignant CLI, the overall balance of clinical, histopathological, immunophenotypic, and molecular features should be considered carefully to establish a diagnosis. Despite advances in ancillary studies such as immunohistochemistry and molecular clonality, these studies often display specificity and sensitivity limitations. Therefore, proper clinicopathological correlation still remains the gold standard for the precise diagnosis of CLIs.

  12. Human natural killer cell development in secondary lymphoid tissues

    Science.gov (United States)

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  13. Total lymphoid irradiation in the Wistar rat: technique and dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Hoogenhout, J.; Kazem, I.; de Jong, J.

    1983-01-01

    The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetery, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments.

  14. Classificação da Organização Mundial da Saúde para os tumores dos tecidos hematopoético e linfoide, 4ª edição, 2008: principais modificações introduzidas em relação à 3ª edição, 2001 World Health Organization classification of tumors of hematopoietic and lymphoid tissues, 4th edition, 2008: major changes from the 3rd edition, 2001

    Directory of Open Access Journals (Sweden)

    Maria Claudia Nogueira Zerbini

    2011-02-01

    Full Text Available A Classificação da Organização Mundial da Saúde (OMS para os tumores do tecido hematopoético e linfoide (4ª edição, 2008¹ representa uma atualização da 3ª edição, 2001². Apresentamos a seguir um resumo dessas alterações nos grupos das doenças mieloproliferativas, mileodisplásicas, leucemias mieloides agudas, neoplasias de células precursoras B e T, e neoplasias de células B, T e NK maduras. O entendimento das alterações genético-moleculares e os resultados alcançados com propostas terapêuticas inovadoras nesses grupos de doenças demandam constante reavaliação de sua classificação, justificando as alterações importantes aqui discutidas1,3-5.The World Health Organization (WHO Classification of tumors of hematopoietic and lymphoid tissues (4th edition, 2008¹ presents an updated version of the 3rd edition published in 2001². A summary of these changes relates to the groups of chronic myeloproliferative disorders, myelodisplasia, acute myeloid leukemias, neoplasms of precursor B and T cells and neoplasms derived of mature B, T and NK cells. A better understanding of molecular genetic changes and results achieved with innovative therapeutic approaches in these groups of diseases requires constant reassessment of the classifications, supporting the major changes discussed here, including interesting comments from literature1, 3-5.

  15. Advanced chronic lymphoid leukemia with severe bronchopneumonia: an Autopsy Case Report

    Science.gov (United States)

    Amaral, Felipe Gomes Campos; Lima, Luiz Guilherme Cernaglia Aureliano; Hatanaka, Veruska Menegatti Anastacio; Siqueira, Sheila Aparecida Coelho

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasia with the B immunophenotype, which corresponds to the leukemic form of lymphocytic lymphoma. This entity is characterized, in most cases, by immunosuppression due to impaired function of immune cells, hypogammaglobulinemia, bone marrow infiltration, and immune dysfunction due to the neoplasia and the chemotherapy, when prescribed. We describe the case of a 63-year-old woman with a previous diagnosis of advanced CLL, refractory to treatment, who presented respiratory failure at the emergency department and died soon after hospital admission. The autopsy examination showed a large retroperitoneal mass compressing large vessels and abdominal and pelvic organs; generalized lymphadenopathy; and liver, spleen, bone marrow, heart and kidney infiltration. A Gram-negative bacilli bronchopneumonia with diffuse alveolar damage was detected, which was likely to be the immediate cause of death. PMID:27284536

  16. Diffuse Nodular Lymphoid Hyperplasia of the Intestine Caused by Common Variable Immunodeficiency and Refractory Giardiasis.

    Science.gov (United States)

    Choi, Jung Hye; Han, Dong Soo; Kim, Jieun; Yi, Kijong; Oh, Young-Ha; Kim, Yongsoo

    2017-01-01

    Diffuse nodular lymphoid hyperplasia of the gastrointestinal tract is a rare disease characterized by numerous small polypoid nodules in the small intestine, large intestine, or both. It is associated with immunodeficiency and infection, such as Giardia lamblia and Helicobacter pylori. Although diffuse nodular lymphoid hyperplasia associated with common variable immunodeficiency (CVID) and giardiasis is already known, a few studies have reported a regression of the lymphoid nodules after the eradication of infection. We herein describe a case of diffuse nodular lymphoid hyperplasia of the intestine associated with CVID and refractory giardiasis that markedly improved after successfully treating giardiasis.

  17. Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Magliozzi, Roberta; Columba-Cabezas, Sandra; Serafini, Barbara; Aloisi, Francesca

    2004-03-01

    Given the abnormalities in B-cell activity occurring in the central nervous system (CNS) of patients with multiple sclerosis (MS), we have explored the possibility that CNS inflammation induced in mouse models of experimental autoimmune encephalomyelitis (EAE) triggers expression of molecules that control the development and functional organization of lymphoid follicles, the sites where B-cell responses are initiated. By reverse transcription-polymerase chain reaction (RT-PCR), we find that gene expression of CXCL13, a chemokine involved in B-cell recruitment into lymphoid follicles, and BAFF, a key regulator of B-cell survival, is markedly and persistently upregulated in the CNS of mice with relapsing-remitting and chronic-relapsing EAE. Using immunohistochemical techniques, we also show the presence of lymphoid follicle-like structures containing B cells and a reticulum of CXCL13+ and FDC-M1+ follicular dendritic cells within the meninges of several mice undergoing progressive relapsing EAE. These observations indicate that, under chronic inflammatory conditions, the less immunoprivileged meningeal compartment is the site where ectopic lymphoid follicles preferentially develop and where pathogenic B-cell responses could be sustained in autoimmune disorders of the CNS.

  18. MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets.

    Science.gov (United States)

    Ooi, A G Lisa; Sahoo, Debashis; Adorno, Maddalena; Wang, Yulei; Weissman, Irving L; Park, Christopher Y

    2010-12-14

    MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1(lo)CD34(-) lymphoid-balanced and the Slamf1(neg)CD34(-) lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8(+) T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC.

  19. Lymphoid follicles in children with Helicobacter pylori-negative gastritis

    Science.gov (United States)

    Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim

    2017-01-01

    Purpose The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Patients and methods Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. Results A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, pgastritis and lymphoid follicles were associated most commonly with H. pylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Conclusion Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status. PMID:28860835

  20. Immunomodulation of gut-associated lymphoid tissue: current perspectives.

    Science.gov (United States)

    Luongo, Diomira; D'Arienzo, Rossana; Bergamo, Paolo; Maurano, Francesco; Rossi, Mauro

    2009-01-01

    The gut-associated lymphoid tissue is deputed both to protect from infectious diseases and to evoke immune tolerance. Efficient responses need mucosal adjuvants: starting from cholera toxin, new variants of cholera toxin were developed depleted of toxicity. In addition, lipid colloidal particles, bacterial DNA, and probiotics have been experimented. Tolerance is currently induced by means of the B subunit of cholera toxin, whereas new strategies encompass the use of probiotics, expansion of regulatory T cells and blocking of paracellular entry of antigens. Finally, we report different approaches developed for celiac disease, an immune-mediated disease whose triggering antigen is known.

  1. Possible relationship between mercury retention and resistance to lymphoid leukosis

    Energy Technology Data Exchange (ETDEWEB)

    Miller, V.L.; Bearse, G.E.; McClary, C.F.; Csonka, E.

    1969-01-01

    An attempt is made to investigate the retention of mercury by resistant and susceptible chicks from four separate selective breeding programs. Four to eight week old chicks, weighing approximately 300-700 g., were injected intramuscularly with 3.0 mg. mercury per kg body weight as mercuric chloride or as pheynlmercuric acetate. After 96 hours the chicks were killed and the livers and kidneys excised and analyzed for mercury. Results revealed that chicks resistant to lymphoid leukosis retained larger amounts of mercury from mercuric chloride or phenylmercuric acetate injections than susceptible chicks.

  2. Effect of total lymphoid irradiation in chronic progressive multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cook, S.D.; Devereux, C.; Troiano, R.; Hafstein, M.P.; Zito, G.; Hernandez, E.; Lavenhar, M.; Vidaver, R.; Dowling, P.C.

    1986-06-21

    Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI has less functional decline than sham-irradiated MS patients (p<0.01). A significant relation was noted between absolute blood lymphocyte counts in the first year after TLI and subsequent course, patients with higher lymphocyte counts generally having a worse prognosis (p<0.01). TLI was well tolerated and associated with only mild short-term, and to date, long-term side-effects.

  3. Contribuição dos depósitos hepáticos de imunoglobulina A no diagnóstico da hepatopatia alcoólica Contribution of hepatic immunoglobulin A deposits to the diagnosis of alcoholic hepatopathy

    Directory of Open Access Journals (Sweden)

    Luiz Edmundo MAZZOLENI

    2001-09-01

    Full Text Available Racional — A doença hepática alcoólica é enfermidade grave e freqüente e o seu diagnóstico nem sempre é fácil. Objetivo — Avaliar a contribuição de depósitos de imunoglobulina A (IgA nos sinusóides hepáticos para o diagnóstico da hepatopatia alcoólica. Casuística e Método — Foi estudada a presença de imunoglobulina A por imunofluorescência direta em 59 pacientes submetidos a punção biopsia hepática, indicada por alterações clínicas ou laboratoriais sugestivas de hepatopatia crônica. Resultados — Constatou-se deposição significativa de imunoglobulina A hepática em alcoolistas, em comparação com os não-alcoolistas, com sensibilidade de 76% (IC95%: 54,5-89,8 e especificidade de 73,5% (IC95%: 55,3-86,5. Em indivíduos que apresentavam só o álcool como agente etiológico da hepatopatia, comparados com o grupo de portadores dos vírus B e C, os resultados foram ainda mais significativos, com sensibilidade de 85,7% (IC95%: 56,2-97,5 e especificidade de 89,5% (IC95%: 65,5%-98,2%. Conclusão — A deposição de imunoglobulina A nos sinusóides hepáticos apresenta sensibilidade e especificidade para o diagnóstico da lesão hepática induzida pelo álcool. Esse recurso pode ser particularmente útil quando a histologia convencional não consegue definir a causa específica da alteração encontrada.Background — Alcoholic hepatic disease is a severe and frequent disease and its diagnosis is not always an easy task. Aim — To assess the contribution of immunoglobulin A (IgA in the hepatic sinusoids for diagnosis of alcoholic hepatopathy. Patients and method — The presence of IgA was studied through direct immunofluorescence in 59 patients submitted to hepatic needle biopsy, indicated by clinical or in vitro changes suggestive of chronic hepatopathy. Results — A significant deposition of IgA was found in alcoholic patients as compared to non-alcoholic patients, with 76% sensitivity (95%CI: 54.5-89.8 and 73

  4. Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

    Energy Technology Data Exchange (ETDEWEB)

    Sakaguchi, N.; Sakaguchi, S. (Stanford Univ. School of Medicine, CA (United States) Scripps Research Institute, La Jolla, CA (United States) PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki (Japan)); Miyai, K. (Univ. of California, San Diego, LA Jolla, CA (United States))

    1992-11-01

    Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.

  5. Expression of HOX C homeobox genes in lymphoid cells.

    Science.gov (United States)

    Lawrence, H J; Stage, K M; Mathews, C H; Detmer, K; Scibienski, R; MacKenzie, M; Migliaccio, E; Boncinelli, E; Largman, C

    1993-08-01

    The class I homeobox genes located in four clusters in mammalian genomes (HOX A, HOX B, HOX C, and HOX D) appear to play a major role in fetal development. Previous surveys of homeobox gene expression in human leukemic cell lines have shown that certain HOX A genes are expressed only in myeloid cell lines, whereas HOX B gene expression is largely restricted to cells with erythroid potential. We now report a survey of the expression patterns of 9 homeobox genes from the HOX C locus in a panel of 24 human and 7 murine leukemic cell lines. The most striking observation is the lymphoid-specific pattern of expression of HOX C4, located at the 3' end of the locus. A major transcript of 1.9 kilobases is observed in both T-cell and B-cell lines. HOX C4 expression is also detected in normal human marrow and peripheral blood lymphocytes, but not in mature granulocytes or monocytes. HOX C8 is also expressed in human lymphoid cells but is expressed in other blood cell types as well. However, the HOX C8 transcript pattern is lineage specific. These data, in conjunction with earlier findings, suggest that homeobox gene expression influences lineage determination during hematopoiesis.

  6. Increased lymphoid tissue apoptosis in baboons with bacteremic shock.

    Science.gov (United States)

    Efron, Philip A; Tinsley, Kevin; Minnich, Douglas J; Monterroso, Victor; Wagner, J; Lainée, Pierre; Lorré, Katrien; Swanson, Paul E; Hotchkiss, Richard; Moldawer, Lyle L

    2004-06-01

    The molecular mechanisms of immune cell apoptosis during sepsis remain unclear. Two young adult baboons (Papio sp.) received a lethal dose of live Escherichia coli and were sacrificed at either 16 (for animal welfare concerns) or 24 h post-septic shock. An additional baboon, which received no bacteria, served as a control. Necropsy was performed immediately with subsequent immunohistochemical staining of lymphoid tissue. Immunohistologic analysis of tissues from the septic baboons revealed marked systemic lymphocyte apoptosis occurring in all lymphoid tissues examined. Focally, pyknotic and karyorrhectic lymphocytes demonstrated activation of a mitochondrial-dependent cell death pathway (active caspase 9 and apoptosis-inducing factor). Other regions demonstrated apoptotic lymphocytes with activation of a death receptor-dependent cell pathway (Fas ligand). Thus, we have demonstrated for the first time in primates that overwhelming gram-negative bacteremia produces an early and profound lymphocyte death that occurs through multiple cell death pathways. Bacteremic shock in the baboon may be an appropriate model for studying experimental therapies aimed at blocking lymphocyte apoptosis because their response appears comparable to humans dying from sepsis.

  7. TH2, allergy and group 2 innate lymphoid cells.

    Science.gov (United States)

    Licona-Limón, Paula; Kim, Lark Kyun; Palm, Noah W; Flavell, Richard A

    2013-06-01

    The initiation of type 2 immune responses by the epithelial cell-derived cytokines IL-25, IL-33 and TSLP has been an area of extensive research in the past decade. Such studies have led to the identification of a new innate lymphoid subset that produces the canonical type 2 cytokines IL-5, IL-9 and IL-13 in response to IL-25 and IL-33. These group 2 or type 2 innate lymphoid cells (ILC2 cells) represent a critical source of type 2 cytokines in vivo and serve an important role in orchestrating the type 2 response to helminths and allergens. Further characterization of ILC2 cell biology will enhance the understanding of type 2 responses and may identify new treatments for asthma, allergies and parasitic infections. Interactions between ILC2 cells and the adaptive immune system, as well as examination of potential roles for ILC2 cells in the maintenance of homeostasis, promise to be particularly fruitful areas of future research.

  8. Lymphoid follicles in children with Helicobacter pylori-negative gastritis.

    Science.gov (United States)

    Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim

    2017-01-01

    The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, ppylori-positive group (ppylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status.

  9. [Immunoglobulin genes in lymphoid cells and regulation of their transcription].

    Science.gov (United States)

    Stepchenko, A G; Urakov, D N; Luchina, N N; Deev, S M; Polianovskiĭ, O L

    1990-01-01

    The hybridoma genomes contain polyploid sets of immunoglobulin genes. We have shown, that the hybridoma PTF-02 genome contains three genes of heavy chains and two genes of light chains. The genes responsible for antibody synthesis were cloned and their structure were determined. Investigation of the kappa gene transcription and its fragments which contain regulatory sequences revealed a nuclear factor. The latter interacts with the octanucleotide localized at the promoter region of the kappa gene. The purified factor activates the transcription of the kappa gene in a heterologous cell-free system. Together with the tissue-specific factor there is also an universal factor interacting with the octanucleotide sequence. We have shown an additional factor in lymphoid cells interact with the protein which binds to the octanucleotide sequence. We have shown an additional factor in lymphoid cells interacting with the protein which binds to the octanucleotide sequence. As a result, there is a family of factors which interact with ATTTGCAT sequence. One major factor (m.w. 60 +/- 2 kDa) is an obligatory component for the initiation of immunoglobulin genes transcription.

  10. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Field, E.H.; Strober, S.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.L.; Tanay, A.S.; Calin, H.J.; Terrell, C.P.; Kaplan, H.S.

    1983-08-01

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.

  11. MicroRNAs in mouse models of lymphoid malignancies

    Directory of Open Access Journals (Sweden)

    Nicola A. O. Zanesi

    2010-05-01

    Full Text Available The discovery of microRNAs (miRNAs has revealed a new layer of gene expression regulation that affects many normal and pathologic biological systems. Among the malignancies affected by the dysregulation of miRNAs there are cancers of lymphoid origin, in which miRNAs are thought to have tumor suppressive or tumor promoting activities, depending on the nature of their specific targets. In the last 4-5 years, the experimental field that provided the deepest insights into the in vivo biology of miRNAs is that of mouse modeling in which transgenic and knockout animals mimic, respectively, over-expression or down-regulation of specific miRNAs involved in human leukemia/lymphoma. This review discusses recent advances in our understanding of lymphoid malignancies based on the natural and engineered mouse models of three different miRNAs, miR-15a/16-1 cluster, miR-155, and miR-17-92 cluster.

  12. Occult pulmonary mucosa-associated lymphoid tissue lymphoma presenting as catastrophic antiphospholipid antibody syndrome.

    Science.gov (United States)

    Regunath, Hariharan; Shortridge, James; Raza, Shahzad; Nistala, Puja; Huffman, Brandon M; Wang, Michael X; Xiang, Dong

    2013-11-01

    Catastrophic antiphospholipid antibody syndrome (CAPS) is characterized by fulminant thrombosis of the arterial and venous beds of multiple organ systems over a relatively short period of time and with a high mortality rate. Mucosa-associated lymphoid tissue (MALT) lymphoma of the lung has never been reported as a causative or precipitating factor for CAPS in the CAPS registry database. The present study describes a rare case of pulmonary MALT lymphoma of the lung that presented as CAPS. A 19-year-old Hispanic female presented with shortness of breath and abdominal pain. Computed tomography (CT) scans of the chest and abdomen revealed multiple portal vein thromboses and bilateral pulmonary nodules. Within one week of presentation, the patient developed a straight sinus thrombosis and upper extremity deep vein thrombosis, which led to shortness of breath. A biopsy of the lung nodule revealed MALT lymphoma. The present case illustrates a rarely reported pulmonary MALT lymphoma presenting as CAPS in a young female. The patient was successfully treated with 90 mg/m(2) bendamustine on days one and two and rituximab 375 mg/m(2) on day one of each 28-day cycle. Complete remission of the lung nodules was observed following three cycles of treatment, as visualized by positron emission tomography (PET)/CT scan. Fondaparinux was identified as a feasible anticoagulation drug of choice for this case. At seven months post-treatment, the patient continues to be stable with no further evidence of thrombosis and is currently undergoing rituximab maintenance therapy every six months for two years. A repeat lupus anticoagulant antibody assay turned and remained negative during the clinical follow-up period. A prompt diagnosis and early aggressive treatment is potentially curative and may dramatically decrease the mortality risk. Future studies should explore the role of rituximab in the management of CAPS-associated B-cell lymphoid malignancies.

  13. Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Schreuder, B.E.C.; Meloen, R.H.; Mooij-Harkes, G.; Vromans, M.E.W.; Langeveld, J.P.M.

    1996-01-01

    The scrapie-associated form of the prion protein (PrP(Sc)) accumulates in the brain and lymphoid tissues of sheep with scrapie. In order to assess whether detecting PrP(Sc) in lymphoid tissue could he used as a diagnostic test for scrapie, we studied the localization and distribution of PrP(Sc) in v

  14. [Histopathological Study of the Relationship between Lymphoid Follicles and Different Endoscopic Types of Nodular Gastritis].

    Science.gov (United States)

    Nagata, Takuo; Ishitake, Hisahito; Shimamoto, Fumio; Tamura, Tadamasa; Matsumura, Kazunori; Sumii, Masaharu; Nakai, Shirou

    2014-11-01

    Nodular gastritis is characterized histologically by hyperplasia and enlargement of lymphoid follicles in the lamina propria. With the objective of elucidating the relationship between different endoscopic types of nodular gastritis and lymphoid follicles, distributions of lymphoid follicles in the lamina propria were investigated in young gastric cancer patients with nodular gastritis. For the study, whole-mucosal step sectioning of each resected stomach was performed, the densities of lymphoid follicles of all specimens were measured microscopically, and the horizontal and depth distributions were calculated. For assessment in the horizontal direction, density distribution diagrams of lymphoid follicles were created. For assessment in the depth direction, the different endoscopic types of nodular gastritis were compared in the five different analysis sites. In the assessment of the horizontal distribution, no characteristic distribution tendencies were observed in either the granular type group or the scattered type group; however, it was found that areas with relatively high densities of lymphoid follicles generally coincided with the areas where nodular gastritis was observed endoscopically. These results suggested that hyperplasia and aggregation of lymphoid follicles in the lamina propria are involved at the sites where nodular gastritis is observed endoscopically. In the assessment of the depth distribution, lymphoid follicles tended to be more unevenly distributed in the upper lamina propria in the granular type group than in the scattered type at the three different analysis sites where nodular gastritis was observed endoscopically. These results suggested the possibility of a granular type characteristic.

  15. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen

    DEFF Research Database (Denmark)

    Rodrigues, Celso Arrais; Rocha, Vanderson; Dreger, Peter;

    2014-01-01

    We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an...

  16. Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas

    NARCIS (Netherlands)

    R.J. Bende; F. van Maldegem; C.J.M. van Noesel

    2009-01-01

    Chronic autoimmune or pathogen-induced immune reactions resulting in lymphoid neogenesis are associated with development of malignant lymphomas, mostly extranodal marginal zone B-cell lymphomas (MZBCLs). In this review we address (i) chemokines and adhesion molecules involved in lymphoid neogenesis;

  17. Gata3 drives development of RORγt+ group 3 innate lymphoid cells

    NARCIS (Netherlands)

    N. Serafini (Nicolas); R.G.J. Klein Wolterink (Roel); N. Satoh-Takayama (Naoko); W. Xu (Weiwei); C.A. Vosshenrich (Christian); R.W. Hendriks (Rudi); J.P. di Santo (James)

    2014-01-01

    textabstractGroup 3 innate lymphoid cells (ILC3) include IL-22-producing NKp46+ cells and IL-17A/IL-22-producing CD4+ lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and

  18. Cells involved in the immune response. XXIX Establishment of optimal conditions for the primary and secondary immune responses by rabbit lymphoid cells in vitro.

    Science.gov (United States)

    Richter, M; Behelak, Y

    1975-01-01

    Attempts were made to initiate the primary and secondary humoral immune responses to sheep red blood cells (SRBC) in vitro as determined by the hemolytic plaque-forming cell (PFC) response, with cell suspensions prepared from a variety of lymphoid organs of the rabbit- thymus, bone marrow, spleen, appendix, sacculus rotundus, Peyer's patches, popliteal lymph node and circulating leukocytes. A number of different media and gaseous phases were utilized in order to establish the optimal conditions for the immune response in vitro. The induction of a secondary PFC response was consistently obtained with 'memory' spleen cells obtained from rabbits 3-6 months following intravenous immunization with SRBC but not with cells of any of the other lymphoid organs, and this response probably represents the activity of memory cells which reside in the rabbit spleen. A primary response was observed only with 'normal' spleen cells, and the medium which faciliated the response was different from that which facilitated the induction of the secondary response in vitro. It was also observed, using a medium in which normal spleen cells were incapable of generating PFC', that mixed cultures of normal spleen and normal appendix or bone marrow cells could give a marked PFC reponse in vitro. Whether the PFC response to SRBCs obtained with the lymphoid cells of normal, unimmunized rabbits represent a true primary response, a secondary response, or a response of a different nature as a consequence of continuous subthreshold immunization of the rabbit with enteric microorganisms which cross-react with the antigen, remains to be determined. However, out initial successes with cultures consisting of cells of at least two distinct lymphoid organs in cases where the cells of any one of these organs could not respond, suggest that interaction of at least two functionally distinct cells is required and that the repsonse observed in vitro is probably a primary immune response.

  19. Reactive lymphoid hyperplasia of the liver mimicking hepatocellular carcinoma: incidental finding of two cases.

    Science.gov (United States)

    Lv, Ang; Liu, Wendy; Qian, Hong-Gang; Leng, Jia-Hua; Hao, Chun-Yi

    2015-01-01

    Reactive lymphoid hyperplasia is a rare disease that forms a mass-like lesion and is characterized by the proliferation of non-neoplastic, polyclonal lymphocytes forming follicles. We recently encountered 2 cases of reactive lymphoid hyperplasia of liver, both of which were asymptomatic and mimicked hepatocellular carcinoma by various imaging modalities. Based on the clinical impression of hepatocellular carcinoma, surgical resections were performed. Microscopic findings revealed that both lesions consisted of an aggregation of lymphocytes consisting of predominantly B-cells, with multiple lymphoid follicles positive for CD10 and negative for bcl-2, consistent with the diagnosis of reactive lymphoid hyperplasia. Polyclonality of both lesions was further confirmed by B cell receptor gene rearrangement study. The incidence of reactive lymphoid hyperplasia in the liver is exceedingly rare, and it is difficult to differentiate such lesions from hepatic malignancies based upon clinical grounds. The clinicopathological findings and literature review of this report may be helpful to improve the clinical decision-making.

  20. Lymphoid papillary hyperplasia of the palatine tonsil: a Chinese case report.

    Science.gov (United States)

    Zhao, Ming; Yu, Jingjing; Li, Changshui

    2013-01-01

    Lymphoid papillary hyperplasia is a rare abnormality of the tonsils with a predilection for affecting young Asian girls. Herein, we report a 31-year-old Chinese woman presented as right lateral recurrent tonsillar hypertrophy with odynophagia and dysphagia over the past 5 years, worsening over a period of for half a year. Clinically, this lesion was similar to papillomatosis or lymphoid polyposis. However, histopathologic study showed a distinctive form of lymphoid hyperplasia with considerable distinct finger-like projections composed of many phyllodes which contained remarkable follicular lymphoid hyperplasia. This is the only Chinese case of lymphoid papillary hyperplasia of the palatine tonsils that has been reported in the most recent English literature so far. The importance of recognizing this disorder rests in the fact that in spite of the clinical features suggestive of both a benign and a malignant tumor, however, the process is a benign tumor-like proliferation, probably non-neoplastic, could easily be cured by tonsillectomy.

  1. Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1.

    Science.gov (United States)

    Sarig, Ofer; Goldsher, Dorit; Nousbeck, Janna; Fuchs-Telem, Dana; Cohen-Katsenelson, Ksenya; Iancu, Theodore C; Manov, Irena; Saada, Ann; Sprecher, Eli; Mandel, Hanna

    2013-09-01

    3-Methylglutaconic aciduria (3-MGCA) type IV is defined as a heterogeneous group of inborn errors featuring in common 3-MGCA and associated with primary mitochondrial dysfunction leading to a spectrum of multisystem conditions. We studied four patients who presented at birth with a clinical picture simulating a primary mitochondrial hepatic disorder consistent with the MEGDEL syndrome including 3-MGCA, sensorineural deafness, encephalopathy and a brain magnetic resonance imaging with signs of Leigh disease. All affected children displayed biochemical features consistent with mitochondrial OXPHOS dysfunction including hepatic mitochondrial DNA depletion in one patient. Homozygosity mapping identified a candidate locus on 6q25.2-6q26. Using whole exome sequencing, we identified two novel homozygous mutations in SERAC1 recently reported to harbor mutations in MEGDEL syndrome. Both mutations were found to lead to decreased or absent expression of SERAC1. The present findings indicate that infantile hepatopathy is a cardinal feature of MEGDEL syndrome. We thus propose to rename the disease MEGDHEL syndrome. Copyright © 2013 Wiley Periodicals, Inc.

  2. Molecular pathogenesis and histologic and clinical features of extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue type.

    NARCIS (Netherlands)

    Kuper-Hommel, M.J.; Krieken, J.H.J.M. van

    2012-01-01

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type (EMZL) is considered an antigen driven lymphoid malignancy associated with protracted antigenic stimulation by microbial pathogens, auto-antigens or other unknown stimuli, which trigger a sustained lymphoid proliferat

  3. KINETICS OF B-CELL SUBPOPULATIONS IN PERIPHERAL LYMPHOID-TISSUES - EVIDENCE FOR THE PRESENCE OF PHENOTYPICALLY DISTINCT SHORT-LIVED AND LONG-LIVED B-CELL SUBSETS

    NARCIS (Netherlands)

    DEENEN, GJ; KROESE, FGM

    1993-01-01

    A small proportion of the sIg+ B lymphocytes in peripheral lymphoid organs [22% in spleen and 6% in lymph node (LN)] in rat carries the Thy-1 antigen. These Thy-1 + B cells represent newly formed bone marrow (BM) derived (or immature) B cells. In this study we investigated the kinetic behavior of Th

  4. Peyer's patch innate lymphoid cells regulate commensal bacteria expansion.

    Science.gov (United States)

    Hashiguchi, Masaaki; Kashiwakura, Yuji; Kojima, Hidefumi; Kobayashi, Ayano; Kanno, Yumiko; Kobata, Tetsuji

    2015-05-01

    Anatomical containment of commensal bacteria in the intestinal mucosa is promoted by innate lymphoid cells (ILCs). However, the mechanism by which ILCs regulate bacterial localization to specific regions remains unknown. Here we show that Peyer's patch (PP) ILCs robustly produce IL-22 and IFN-γ in the absence of exogenous stimuli. Antibiotic treatment of mice decreased both IL-22+ and IFN-γ+ cells in PPs. Blockade of both IL-2 and IL-23 signaling in vitro lowered IL-22 and IFN-γ production. PP ILCs induced mRNA expression of the antibacterial proteins RegIIIβ and RegIIIγ in intestinal epithelial cells. Furthermore, in vivo depletion of ILCs rather than T cells altered bacterial composition and allowed bacterial proliferation in PPs. Collectively, our results show that ILCs regulate the expansion of commensal bacteria in PPs.

  5. T-cell-predominant lymphoid hyperplasia in a tattoo*

    Science.gov (United States)

    Souza, Erica Sales; Rocha, Bruno de Oliveira; Batista, Everton da Silva; de Oliveira, Rodrigo Ferreira; Farre, Lourdes; Bittencourt, Achilea Lisboa

    2014-01-01

    Cutaneous lymphoid hyperplasia (CLH) can be idiopathic or secondary to external stimuli, and is considered rare in tattoos. The infiltrate can be predominantly of B or T-cells, the latter being seldom reported in tattoos. We present a case of a predominantly T CLH, secondary to the black pigment of tattooing in a 35-year-old patient, with a dense infiltrate of small, medium and scarce large T-cells. Analysis of the rearrangement of T-cells receptor revealed a polyclonal proliferation. Since the infiltrate of CLH can simulate a T lymphoma, it is important to show that lesions from tattoos can have a predominance of T-cells. PMID:25387518

  6. Prevalence and aetiology of anaemia in lymphoid malignancies.

    Science.gov (United States)

    Ghosh, J; Singh, R K Bikramjit; Saxena, R; Gupta, R; Vivekanandan, S; Sreenivas, V; Raina, V; Sharma, A; Kumar, L

    2013-01-01

    We prospectively studied the prevalence, type and causes of anaemia in newly diagnosed patients with lymphoid malignancies. Between January 2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15 years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia with anaemia (haemoglobin anaemia. Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients, respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%) patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%) patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in 5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients. Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to bone marrow involvement was present in 16/40 (40%). In most patients with bone marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia was attributable to bone marrow involvement alone. Anaemia was multifactorial in 18/46 (39.1%) patients. Nutritional deficiency alone or in combination was present in 22/46 (47.8%) patients. Anaemia is common in lymphoid malignancies at initial presentation. Besides managing anaemia of chronic disease and bone marrow involvement, nutritional and autoimmune causes should be ruled out. Copyright 2013, NMJI.

  7. Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine

    Energy Technology Data Exchange (ETDEWEB)

    Knechtle, S.J.; Halperin, E.C.; Saad, T.; Bollinger, R.R.

    1986-05-01

    Total lymphoid irradiation and cyclosporine have profound immunosuppressive properties and permit successful heart allotransplantation. Cyclosporine used alone has not permitted consistently successful transplantation between species in all cases. Total lymphoid irradiation has not been applied to xenotransplantation. The efficacy of total lymphoid irradiation alone and in combination with cyclosporine was examined using an animal model of heart xenotransplantation. Heterotopic heart transplants were performed using inbred Syrian hamsters as donors and Lewis rats as recipients. Total lymphoid irradiation was administered preoperatively over 3 weeks for a total dose of 15 gray. Cyclosporine was started on the day of surgery and was given as a daily intramuscular injection of 2.5, 5, or 10 mg/kg/day until rejection was complete. Neither total lymphoid irradiation nor cyclosporine alone markedly prolonged graft survival. However, combined total lymphoid irradiation and cyclosporine, 5 or 10 mg/kg/day, dramatically prolonged graft survival to greater than 100 days in most recipients. There were no treatment-related deaths. In conclusion, combined total lymphoid irradiation and cyclosporine permit successful long-term survival of heart xenotransplants in this hamster-to-rat model.

  8. Characterizing natural hydrogel for reconstruction of three-dimensional lymphoid stromal network to model T-cell interactions.

    Science.gov (United States)

    Kim, Jiwon; Wu, Biming; Niedzielski, Steven M; Hill, Matthew T; Coleman, Rhima M; Ono, Akira; Shikanov, Ariella

    2015-08-01

    Hydrogels have been used in regenerative medicine because they provide a three-dimensional environment similar to soft tissues, allow diffusion of nutrients, present critical biological signals, and degrade via endogenous enzymatic mechanisms. Herein, we developed in vitro system mimicking cell-cell and cell-matrix interactions in secondary lymphoid organs (SLOs). Existing in vitro culture systems cannot accurately represent the complex interactions happening between T-cells and stromal cells in immune response. To model T-cell interaction in SLOs in vitro, we encapsulated stromal cells in fibrin, collagen, or fibrin-collagen hydrogels and studied how different mechanical and biological properties affect stromal network formation. Overall, fibrin supplemented with aprotinin was superior to collagen and fibrin-collagen in terms of network formation and promotion of T-cell penetration. After 8 days of culture, stromal networks formed through branching and joining with other adjacent cell populations. T-cells added to the newly formed stromal networks migrated and attached to stromal cells, similar to the T-cell zones of the lymph nodes in vivo. Our results suggest that the constructed three-dimensional lymphoid stromal network can mimic the in vivo environment and allow the modeling of T-cell interaction in SLOs.

  9. The interbranchial lymphoid tissue of Atlantic Salmon (Salmo salar L) extends as a diffuse mucosal lymphoid tissue throughout the trailing edge of the gill filament

    DEFF Research Database (Denmark)

    Dalum, Alf S; Austbø, Lars; Bjørgen, Håvard

    2015-01-01

    in all gill segments investigated. Numerous major histocompatibility complex class II(+) -cells were distributed uniformly throughout the filament epithelial tissue. Few Ig(+) -cells were detected. Overall, the morphological features and comparable immune gene expression of the previously described ILT......The teleost gill forms an extensive, semipermeable barrier that must tolerate intimate contact with the surrounding environment and be able to protect the body from external pathogens. The recent discovery of the interbranchial lymphoid tissue (ILT) has initiated an anatomical and functional...... investigation of the lymphoid tissue of the salmonid gill. In this article, sectioning of gill arches in all three primary planes revealed an elongation of the ILT outward along the trailing edge of the primary filament to the very distal end, a finding not previously described. This newly found lymphoid tissue...

  10. The evaluation and optimal use of rituximab in lymphoid malignancies

    Directory of Open Access Journals (Sweden)

    Smolewski P

    2012-01-01

    Full Text Available Tadeusz Robak1, Pawel Robak2, Piotr Smolewski21Department of Hematology, 2Experimental Hematology, Medical University of Łódź, Łódź, PolandAbstract: Rituximab is an IgG1, chimeric monoclonal antibody (mAb containing murine light- and heavy-chain variable-region sequences and human constant-region sequences. Rituximab targets the CD20 molecule expressed on normal and malignant B-lymphocytes. At present, rituximab is the most important mAb of clinical value in patients with B-cell lymphoid malignancies. Since approval in 1997, rituximab has become widely used in chronic lymphocytic leukemia (CLL, follicular lymphoma (FL, mantle cell lymphoma (MCL, and diffused large B-cell lymphoma (DLBCL when combined with chemotherapy. Currently, rituximab is commonly combined with first-line chemotherapy for FL and should be offered as maintenance therapy to all appropriate patients with this disease. Randomized Phase III trials demonstrated the superiority of rituximab added to CHOP chemotherapy against CHOP chemotherapy alone in patients with DLBCL. Rituximab alone has limited activity in MCL but can be used in MCL in combination with chemotherapy, despite the benefits not being as impressive as when used against other lymphoma entities. In addition, for the less frequent B-cell lymphomas, small series show considerable activity for most of these entities. Fludarabine and rituximab combination therapies in CLL yielded promising results in several studies. Two large Phase III randomized trials demonstrated the superiority of chemoimmunotherapy with rituximab compared with chemotherapy alone in previously untreated and refractory/relapsed patients with CLL. Therefore, it can be concluded that rituximab, with only few exceptions, can generally be accepted as a standard component of anti B-cell non-Hodgkin's lymphoma therapies. In this review, the pharmacology, mode of action, pharmacokinetics, and current place in the therapy of B-cell lymphoid

  11. LncRNA profiling of human lymphoid progenitors reveals transcriptional divergence of B and T lineages

    Science.gov (United States)

    Casero, David; Sandoval, Salemiz; Seet, Christopher S.; Scholes, Jessica; Zhu, Yuhua; Ha, Vi Luan; Luong, Annie; Parekh, Chintan; Crooks, Gay M.

    2015-01-01

    To elucidate the transcriptional landscape that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitors spanning the earliest stages of B and T lymphoid specification. Over 3000 novel long non-coding RNA genes (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage-specific and more lineage-specific than protein coding patterns. Protein-coding genes co-expressed with neighboring lncRNA genes were enriched for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships between the earliest progenitors in the human bone marrow and thymus. PMID:26502406

  12. Cystic changes in mucosa-associated lymphoid tissue lymphoma of lung: a case report

    Institute of Scientific and Technical Information of China (English)

    MIAO Li-yun; CAI Hou-rong

    2009-01-01

    @@ Mucosa-associated lymphoid tissue (MALT) is a term that describes lymphoid tissue in various sites of the body, such as the gastrointestinal tract, thyroid, breast, lung, salivary glands, eye, and skin. MALT lymphoma of the lung is a subset of primary pulmonary lymphomas which originates from the MALT. Previously reported computed tomographic (CT) features of MALT lymphoma are the presence of consolidation or nodules in the lungs. 1-4

  13. Advances in research of bronchus-associated lymphoid tissue%支气管相关淋巴组织研究进展

    Institute of Scientific and Technical Information of China (English)

    陈华夏; 高金明; 郭子建

    2008-01-01

    Bronchus-associated lymphoid tissue(BALT)constitutes organized lymphoid aggregates that are capable of T-and B-cell responses to inhaled antigens.BALT,located mostly at bifurcations of the bronchus in animals and humans,is present in the fetus and develops rapidly in the presence of antigens.Humoral immune responses elicited by BALT are primarily B cell and immumoglobulin A responses.BALT is considered as a member of the common mucosal immunologic system.%支气管相关淋巴组织(bronchus-associated lymphoid tissue,BALT)是支气管内能够对吸入的抗原发生B细胞和T细胞免疫应答的淋巴细胞集合体.大部分BALT位于人或动物支气管分叉处,具有相对特异的组织特征.BALT 从胎儿期即开始出现,抗原刺激可以加速BALT的发育.BALT引发的体液免疫应答主要是局部B细胞的应答和免疫球蛋白IgA的应答,是黏膜免疫系统的组成部分.

  14. Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis

    Science.gov (United States)

    Lee, Min-Woo; Odegaard, Justin I.; Mukundan, Lata; Qiu, Yifu; Molofsky, Ari B.; Nussbaum, Jesse C.; Yun, Karen; Locksley, Richard M.; Chawla, Ajay

    2014-01-01

    SUMMARY Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2-and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα+ APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PMID:25543153

  15. Successful murine tumor allotransplantation after total lymphoid irradiation.

    Science.gov (United States)

    Hoppe, R T; Dorie, M J

    1982-06-01

    C3H/Km (H-2k) mice were treated with fractionated total lymphoid irradiation (TLI) (17 x 200 rad) and then were inoculated with 3 x 10(6) tumor cells from the EMT6 tumor cell line derived from the BALB/c (H-2d) mouse. One group of mice also received an i.v. infusion of BALB/c bone marrow (3 x 10(7) cells). Tumors in control animals (no TLI) became palpable within 10 days after inoculation, but subsequent tumor regression was rapid, with complete disappearance in all animals by 23 days. Initial tumor growth was exponential in both groups of mice treated with TLI, but tumors regressed after 30 days in the animals treated with TLI alone. In the group treated with TLI and bone marrow infusion exponential tumor growth continued until pulmonary metastases developed and all animals died. The TLI-treated mouse provides a model for tumor allografting. Further development of this model may demonstrate its efficacy in human tumor xenotransplantation.

  16. EVALUATION OF CYTOKINE GENE POLYMORPHISM IN B CELL LYMPHOID MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    E. L. Nazarova

    2014-01-01

    Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

  17. Effects of aflatoxin on lymphoid cells of weanling rat.

    Science.gov (United States)

    Raisuddin; Singh, K P; Zaidi, S I; Saxena, A K; Ray, P K

    1990-08-01

    Aflatoxin (AF), the hepatocarcinogenic food contaminant produced by the Aspergillus flavus group of fungi, is known to interact with various vital processes, including the immune function. Effects of long-term treatment of three dose levels of aflatoxin B1 (AFB1) on lymphoid cells of weanling rats were studied. AFB1 treatment caused a reduction in body weight gain, significantly (P less than 0.01) at the 700 microgram level. There was also a significant decrease in the weight of spleen and thymus in AFB1-treated animals in comparison to control. Similarly, AFB1 depleted cell populations of thymus and bone marrow and WBC and RBC counts. There was a marked reduction in the population and phagocytic capacity of macrophages due to AFB1 administration at dose levels of 350 and 700 micrograms kg-1 body weight. Macromolecular synthesis of DNA, RNA and protein in macrophages was affected, as there was significant inhibition in the incorporation of [3H]-thymidine, [3H]-uridine and [3H]-leucine. The hampered functioning of macrophages may be due to the cytotoxic action of AFB1.

  18. Treatment of experimental myasthenia gravis with total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.

    1988-07-01

    Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.

  19. Enzyme histochemistry of cecal lymphoid tissue during prenatal period of buffalo

    Science.gov (United States)

    Kapoor, Kritima; Singh, Opinder

    2016-01-01

    Aim: This study was designed to elucidate the histoenzymic distribution of enzymes, i.e., phosphatases, oxidoreductases, dehydrogenases, and diaphorases in cecal lymphoid tissue during its development in the prenatal period. Materials and Methods: The study was conducted on cecum of 15 buffalo fetuses ranging from 16 cm curved crown-rump length (CVRL) (100 days) to 100 cm CVRL (full term). The fetuses were categorized into three groups based on their CVRL. Results: In Group I, the distribution of enzymes was uniformly weak in developing villi-like projections in cecum and completely absent from submucosa. In Group II, the enzymes showed a moderate to strong activity in epithelium lining tunica mucosa which progressively decreased as the fetus progresses toward late gestational age. However, the intense activity of enzymes was observed in developing lymphoid tissue in this group. In Group III, distribution of enzymes reduced in tunica mucosa of cecum with advancing age, whereas the intense activity was noticed in the developed lymphoid tissue complex. Conclusion: The distribution of enzymes was completely absent from submucosal region in cecum of Group I as there was no lymphoid tissue development at this age. In Group II, the enzymes showed a moderate to strong activity in epithelium lining tunica mucosa which progressively decreased toward late gestational age but an intense activity was observed in developing lymphoid tissue. In Group III, distribution of enzymes reduced in tunica mucosa with advancing age with intense activity noticed in the developed lymphoid tissue complex. PMID:27733804

  20. The Role of TOX in the Development of Innate Lymphoid Cells

    Directory of Open Access Journals (Sweden)

    Corey R. Seehus

    2015-01-01

    Full Text Available TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  1. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    Science.gov (United States)

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life.

  2. The Role of TOX in the Development of Innate Lymphoid Cells.

    Science.gov (United States)

    Seehus, Corey R; Kaye, Jonathan

    2015-01-01

    TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  3. Nodular lymphoid hyperplasia: A marker of low-grade inflammation in irritable bowel syndrome?

    Science.gov (United States)

    Piscaglia, Anna Chiara; Laterza, Lucrezia; Cesario, Valentina; Gerardi, Viviana; Landi, Rosario; Lopetuso, Loris Riccardo; Calò, Giovanni; Fabbretti, Giovanna; Brisigotti, Massimo; Stefanelli, Maria Loredana; Gasbarrini, Antonio

    2016-12-14

    To evaluate the prevalence of nodular lymphoid hyperplasia (NLH) in adult patients undergoing colonoscopy and its association with known diseases. We selected all cases showing NLH at colonoscopy in a three-year timeframe, and stratified them into symptomatic patients with irritable bowel syndrome (IBS)-type symptoms or suspected inflammatory bowel disease (IBD), and asymptomatic individuals undergoing endoscopy for colorectal cancer screening. Data collection included medical history and final diagnosis. As controls, we considered all colonoscopies performed for the aforementioned indications during the same period. One thousand and one hundred fifty colonoscopies were selected. NLH was rare in asymptomatic individuals (only 3%), while it was significantly more prevalent in symptomatic cases (32%). Among organic conditions associated with NLH, the most frequent was IBD, followed by infections and diverticular disease. Interestingly, 31% of IBS patients presented diffuse colonic NLH. NLH cases shared some distinctive clinical features among IBS patients: they were younger, more often female, and had a higher frequency of abdominal pain, bloating, diarrhoea, unspecific inflammation, self-reported lactose intolerance and metal contact dermatitis. About 1/3 of patients with IBS-type symptoms or suspected IBD presented diffuse colonic NLH, which could be a marker of low-grade inflammation in a conspicuous subset of IBS patients.

  4. Nodular lymphoid hyperplasia: A marker of low-grade inflammation in irritable bowel syndrome?

    Science.gov (United States)

    Piscaglia, Anna Chiara; Laterza, Lucrezia; Cesario, Valentina; Gerardi, Viviana; Landi, Rosario; Lopetuso, Loris Riccardo; Calò, Giovanni; Fabbretti, Giovanna; Brisigotti, Massimo; Stefanelli, Maria Loredana; Gasbarrini, Antonio

    2016-01-01

    AIM To evaluate the prevalence of nodular lymphoid hyperplasia (NLH) in adult patients undergoing colonoscopy and its association with known diseases. METHODS We selected all cases showing NLH at colonoscopy in a three-year timeframe, and stratified them into symptomatic patients with irritable bowel syndrome (IBS)-type symptoms or suspected inflammatory bowel disease (IBD), and asymptomatic individuals undergoing endoscopy for colorectal cancer screening. Data collection included medical history and final diagnosis. As controls, we considered all colonoscopies performed for the aforementioned indications during the same period. RESULTS One thousand and one hundred fifty colonoscopies were selected. NLH was rare in asymptomatic individuals (only 3%), while it was significantly more prevalent in symptomatic cases (32%). Among organic conditions associated with NLH, the most frequent was IBD, followed by infections and diverticular disease. Interestingly, 31% of IBS patients presented diffuse colonic NLH. NLH cases shared some distinctive clinical features among IBS patients: they were younger, more often female, and had a higher frequency of abdominal pain, bloating, diarrhoea, unspecific inflammation, self-reported lactose intolerance and metal contact dermatitis. CONCLUSION About 1/3 of patients with IBS-type symptoms or suspected IBD presented diffuse colonic NLH, which could be a marker of low-grade inflammation in a conspicuous subset of IBS patients. PMID:28028368

  5. Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

    Energy Technology Data Exchange (ETDEWEB)

    Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.

    1987-02-01

    Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA.

  6. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

    Directory of Open Access Journals (Sweden)

    Frances Humby

    2009-01-01

    Full Text Available BACKGROUND: Follicular structures resembling germinal centres (GCs that are characterized by follicular dendritic cell (FDC networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA. However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i express activation-induced cytidine deaminase (AID, the enzyme required for somatic hypermutation and class-switch recombination (CSR of Ig genes; (ii support ongoing CSR and ACPA production; and (iii remain functional in a RA/severe combined immunodeficiency (SCID chimera model devoid of new immune cell influx into the synovium. METHODS AND FINDINGS: Using immunohistochemistry (IHC and quantitative Taqman real-time PCR (QT-PCR in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching was observed in synovial grafts expressing FDCs/CD21L

  7. Scrapie-specific pathology of sheep lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases often result in accumulation of disease-associated PrP (PrP(d in the lymphoreticular system (LRS, specifically in association with follicular dendritic cells (FDCs and tingible body macrophages (TBMs of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrP(d was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrP(d within endosomes and lysosomes. In addition, TBMs showed PrP(d in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrP(d is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrP(d/cell membrane interactions occur in different cell types.

  8. Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis

    Science.gov (United States)

    Engelbertsen, Daniel; Foks, Amanda C.; Alberts-Grill, Noah; Kuperwaser, Felicia; Chen, Tao; Lederer, James A.; Jarolim, Petr; Grabie, Nir; Lichtman, Andrew H.

    2015-01-01

    Objective Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results We demonstrate that CD25+ ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr−/−rag1−/− mice. To investigate the role of ILCs in atherosclerosis, ldlr−/−rag1−/− mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or with IL-2/anti-IL-2 complexes that expand CD25+ ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti-IL-2 -treated mice. These IL-2 treated mice had reduced VLDL cholesterol and increased triglycerides compared to controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2-complex-induced eosinophilia but did not change lesion size. Conclusions This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in VLDL cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis. PMID:26494229

  9. Role of Innate Lymphoid Cells in Lung Disease

    Directory of Open Access Journals (Sweden)

    SayedMehran Marashian

    2015-10-01

    Full Text Available  Innate lymphoid cells (ILCs are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages.Three types of ILCs (ILC1, 2 & 3 have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK cells and interferon (IFN-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL-13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated inmucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis.There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD. Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lung diseases.In this review we will focus on the role of ILC2 cells and consider their origin, function,location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD.   

  10. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    Science.gov (United States)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  11. Beyond cancer treatment – a review of total lymphoid irradiation for heart and lung transplant recipients

    Energy Technology Data Exchange (ETDEWEB)

    McKay, Clare, E-mail: clmck7@student.monash.edu; Knight, Kellie A; Wright, Caroline [Department of Medical Imaging and Radiation Sciences, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria (Australia)

    2014-09-15

    Immunosuppressive drugs used in the management of heart and lung transplants have a large monetary and quality of life cost due to their side effects. Total lymphoid irradiation (TLI) is one method of minimising the need for or replacing post-operative immunosuppressive drugs. A literature review was conducted on electronic databases using defined search terms. The aim was to establish the indications for the use of TLI, its advantages and disadvantages and the weaknesses associated with the methods used in related research. Eight articles were located that focused on TLI usage in combating organ rejection. These studies identified that the use of TLI resulted in a reduction in early rejection. One study reported a drop in rejection episodes from 0.46 to 0.14 episodes per patient per month once the TLI was complete. While the short-term prognosis is excellent, the long-term outlook is less positive with an increased risk of organ rejection and myelodysplasia 3.5 years post-TLI. This review reminds us that radiation therapy (RT) is not exclusively indicated for cancer treatment. While TLI cannot replace immunosuppressive drug therapy, it can offer a treatment option for people that cannot tolerate immunosuppressive drugs, or when conventional anti-rejection treatment is no longer viable. Reported long-term complications suggest that TLI should be used with caution. However, this modality should not be overlooked in cases of chronic rejection. Further research is required to establish the efficacy of RT in the treatment of transplant patients who are unsuitable for drug-based anti-rejection therapies.

  12. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

    Directory of Open Access Journals (Sweden)

    Melissa D Clouse

    Full Text Available The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc comes into contact with native prion protein (PrPC and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  13. Cytological Evaluation of Bone Marrow in Normal Laying Hens and those With Lymphoid Leukosis

    Directory of Open Access Journals (Sweden)

    H.I. Al-Sadi and E.Y. Hussein

    Full Text Available The purpose of this study was to evaluate cytologically the bone marrow (and peripheral blood of adult laying hens affected with lymphoid leukosis. Diagnosis of the neoplasm was made on the basis of clinical history, signs and symptoms and pathology. Only histologically confirmed cases were included in the study. Examination of blood smears revealed +2 heterophil toxicity and the presence of large numbers of reactive (blast – transformed lymphocytes. Smears that were prepared from the bone marrow showed increased numbers of hemopoietic cells. The total erythrocyte count (TEC, hemoglobin percentage (Hb% , hemoglobin concentration (Hb conc., packed cell volume (PCV and the mean corpuscular hemoglobin concentration (MCHC values were significantly higher (P<0.01 in hens with lymphoid leukosis than in apparently normal hens. The mean corpuscular volume (MCV and the mean corpuscular hemoglobin (MCH were significantly lower (P< 0.01 in hens with lymphoid leukosis than in apparently normal hens. Results of the leukogram indicated that the total leukocyte count (TLC and the percentage (% of lymphocytes were significantly higher (P < 0.01 in hens with lymphoid leukosis than in apparently normal hens. From results of this study it was concluded that cytological evaluation of bone marrow may prove to be a simple , rapid , and useful tool in the diagnosis of lymphoid leukosis in laying hens. [Veterinary World 2010; 3(11.000: 497-499

  14. Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.

    Science.gov (United States)

    Montaldo, Elisa; Juelke, Kerstin; Romagnani, Chiara

    2015-08-01

    Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are "killer" ILCs, comprising NK cells, and "helper-like" ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program.

  15. Morphometric study of lymphoid cells in mycosis fungoides and its simulators.

    Science.gov (United States)

    Sinha, Arvind Kumar; Singh, Manoj Kumar; Dinda, Amit Kumar; Ramam, M

    2003-01-01

    The distinction of early stages of mycosis fungoides from benign lymphoid disorders of skin is difficult by conventional histological techniques. We studied 10 cases of mycosis fungoides, 10 cases of large plaque parapsoriasis, 10 cases of other benign lymphoid disorders of skin and 5 cases of lymph nodes. Nuclear area, perimeter of the nucleus, nuclear contour index, cytoplasmic area, form factor and nuclear cytoplasmic ratio as well as DNA-ploidy were determined by image analysis. There were statistically significant difference (P value < 0.05) between all parameters except nuclear cytoplasmic ratio of the lymphoid cells of Mycosis Fungoides and benign lymphoid disorders of skin. Aneuploidy was found in 50% cases of Mycosis Fungoides. Histopathological parameters like epidermotropism pautrier micro-abscess and atypical lymphocytic infiltrate in both epidermis and dermis were more marked in aneuploid than diploid cases. So, the determination of nuclear contour index and DNA-ploidy is of importance to differentiate between Mycosis Fungoides and benign lymphoid disorders of skin.

  16. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

    Science.gov (United States)

    Clouse, Melissa D; Shikiya, Ronald A; Bartz, Jason C; Kincaid, Anthony E

    2015-01-01

    The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  17. Organizations

    DEFF Research Database (Denmark)

    Hatch, Mary Jo

    Most of us recognize that organizations are everywhere. You meet them on every street corner in the form of families and shops, study in them, work for them, buy from them, pay taxes to them. But have you given much thought to where they came from, what they are today, and what they might become...... in the future? How and why do they have so much influence over us, and what influences them? How do they contribute to and detract from the meaningfulness of lives, and how might we improve them so they better serve our needs and desires? This Very Short Introductions addresses all of these questions...

  18. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Trentham, D.E. (Harvard Medical School, Boston, MA); Belli, J.A.Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-10-01

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

  19. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-10-22

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

  20. Nfil3 is required for the development of all innate lymphoid cell subsets.

    Science.gov (United States)

    Seillet, Cyril; Rankin, Lucille C; Groom, Joanna R; Mielke, Lisa A; Tellier, Julie; Chopin, Michael; Huntington, Nicholas D; Belz, Gabrielle T; Carotta, Sebastian

    2014-08-25

    Innate lymphoid cell (ILC) populations protect against infection and are essential for lymphoid tissue formation and tissue remodeling after damage. Nfil3 is implicated in the function of adaptive immune lineages and NK cell development, but it is not yet known if Nfil3 regulates other innate lymphoid lineages. Here, we identify that Nfil3 is essential for the development of Peyer's patches and ILC2 and ILC3 subsets. Loss of Nfil3 selectively reduced Peyer's patch formation and was accompanied by impaired recruitment and distribution of lymphocytes within the patches. ILC subsets exhibited high Nfil3 expression and genetic deletion of Nfil3 severely compromised the development of all subsets. Subsequently, Nfil3(-/-) mice were highly susceptible to disease when challenged with inflammatory or infectious agents. Thus, we demonstrate that Nfil3 is a key regulator of the development of ILC subsets essential for immune protection in the lung and gut.

  1. A rear case of multilocular thymic cyst with follicular lymphoid hyperplasia; Radiologic and histopathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Suk; Cha, Eun Jung [Konyang University Hospital, Daejeon (Korea, Republic of)

    2016-06-15

    Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.

  2. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    Science.gov (United States)

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.

  3. Role of Interleukin-10 Gene Promoter Region Polymorphism in the Development of Chronic Lymphoid Leukemia.

    Science.gov (United States)

    Ovsepyan, V A; Gabdulkhakova, A Kh; Shubenkiva, A A; Zotina, E N

    2015-12-01

    Relationship between interleukin-10 (IL-10) gene G-1082A (rs1800896) polymorphism and the risk of development and stages of chronic lymphoid leukemia is studied in ethnic Russian residents of the Kirov region of Russia. Associations of allele -1082A and genotypes (-1082AA/-1082AG) with the risk of chronic lymphoid leukemia are detected (OR=1.39, 95%CI=1.09-1.78 and OR=1.66, 95%CI=1.09-2.54, respectively). In addition, association of 1082AA genotype with late stages of the disease by the moment of diagnosis is detected. These data indicate that IL-10 polymorphism G-1082A may be involved in the pathogenesis of chronic lymphoid leukemia.

  4. HELICOBACTER PYLORI-RELATED GASTRITIS AND LYMPHOID TISSUE HYPERPLASIA IN THE AGED

    Institute of Scientific and Technical Information of China (English)

    高天; 陈晓宇; 胡梅洁

    2003-01-01

    Objective To examine the relationship between Helicobacter pylori-related gastritis and the development of lymphoid tissue hyperplasia in the antral mucosa and to pursue its evolution after eradication of H.pylori in the aged. Methods Gastric antral mucosa biopsy specimens for microscopic study were obtained from 101 chronic gastritis patients over 60 years old with H.pylori-positive in the period from 2000 to 2001, and meanwhile those from 124 H.pylori-positive chronic gastritis patients under the age of 60 served as controls. Four to six weeks after a course of anti-H.pylori therapy, biopsy specimens were again obtained. Lym-phoid follicles and aggregates were counted and other pathologic features were scored according to the updated Sydney System for classification of chronic gastritis. Results The prevalence and density of lymphoid follicles and aggregates were significantly lower in the aged as compared with those in the control group, being 36. 6%(37/101) and 0. 41 vs. 72. 5%(90/124) and 0. 81, respectively(P<0.0001). The prevalence and density of lymphoid follicles and aggregates correlated strongly with the activity and severity of gastric antral mucosal inflammation in both groups. Eradication of H.pylori resulted in a decrease in the prevalence and density of lymphoid follicles and aggregates in both groups, especially in the aged group. Conclusion The prevalence and density of lymphoid follicles and aggregates in gastric antral mucosal biopsies correlated closely with H.phlori infection in the aged, therefore, anti-H.pylori treatment would be of importance to the aged patients infected with H.pylori.

  5. Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

    Science.gov (United States)

    Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

    2014-01-01

    OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia. PMID:24555583

  6. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyun [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Tsai, Nicole [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Liu, An [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen J. [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2014-05-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

  7. Susceptibility of human lymphoid tissue cultured ex vivo to xenotropic murine leukemia virus-related virus (XMRV infection.

    Directory of Open Access Journals (Sweden)

    Marta Curriu

    Full Text Available BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV was generated after a recombination event between two endogenous murine leukemia viruses during the production of a prostate cancer cell line. Although the associations of the XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells in vitro. Since recent studies using animal models for infection have yielded conflicting results, we set out an ex vivo model for XMRV infection of human tonsillar tissue to determine whether XMRV produced by 22Rv1 cells is able to replicate in human lymphoid organs. Tonsil blocks were infected and infection kinetics and its pathogenic effects were monitored RESULTS: XMRV, though restricted by APOBEC, enters and integrates into the tissue cells. The infection did not result in changes of T or B-cells, immune activation, nor inflammatory chemokines. Infectious viruses could be recovered from supernatants of infected tonsils by reinfecting DERSE XMRV indicator cell line, although these supernatants could not establish a new infection in fresh tonsil culture, indicating that in our model, the viral replication is controlled by innate antiviral restriction factors. CONCLUSIONS: Overall, the replication-competent retrovirus XMRV, present in a high number of laboratories, is able to infect human lymphoid tissue and produce infectious viruses, even though they were unable to establish a new infection in fresh tonsillar tissue. Hereby, laboratories working with cell lines producing XMRV should have knowledge and understanding of the potential biological biohazardous risks of this virus.

  8. B-cell-independent lymphoid tissue infection by a B-cell-tropic rhadinovirus.

    Science.gov (United States)

    Chao, Brittany; Frederico, Bruno; Stevenson, Philip G

    2015-09-01

    Lymphocytes provide gammaherpesviruses with a self-renewing substrate for persistent infection and with transport to mucosal sites for host exit. Their role in the initial colonization of new hosts is less clear. Murid herpesvirus 4 (MuHV-4), an experimentally accessible, B-cell-tropic rhadinovirus (gamma-2 herpesvirus), persistently infects both immunocompetent and B-cell-deficient mice. A lack of B-cells did not compromise MuHV-4 entry into lymphoid tissue, which involved myeloid cell infection. However, it impaired infection amplification and MuHV-4 exit from lymphoid tissue, which involved myeloid to B-cell transfer.

  9. Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tanay, A.; Field, E.H.; Hoppe, R.T.; Strober, S.

    1987-01-01

    Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty-four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells.

  10. Circulating innate lymphoid cells are unchanged in response to DAC HYP therapy.

    Science.gov (United States)

    Gillard, Geoffrey O; Saenz, Steven A; Huss, David J; Fontenot, Jason D

    2016-05-15

    Innate lymphoid cells (ILCs) play an important role in immunity, inflammation, and tissue remodeling and their dysregulation is implicated in autoimmune and inflammatory disorders. We analyzed the impact of daclizumab, a humanized monoclonal anti-CD25 antibody, on circulating natural killer (NK) cells and ILCs in a cohort of multiple sclerosis patients. An increase in CD56(bright) NK cells and CD56(hi)CD16(intermediate) transitional NK cells was observed. No significant change in total ILCs or major ILC subpopulations was observed. These results refine our understanding of the impact of daclizumab on innate lymphoid cell populations.

  11. Benign Lymphoid Hyperplasia of the Tongue Base Causing Upper Airway Obstruction

    Directory of Open Access Journals (Sweden)

    Noah B. Sands

    2011-01-01

    Full Text Available Severe benign lymphoid hyperplasia (LH is unusual in the head and neck region, but the diagnosis of LH is of clinical importance as it may be confused with malignant lymphoma, both on clinical examination and pathologically. While the etiology is poorly understood, a number of previous theories exist, which are included here in the context of a literature review. In this paper we present a case of severe pharyngeal lymphoid hyperplasia causing airway obstruction and requiring tracheotomy and subsequent surgical debulking.

  12. A novel lymphoid progenitor cell population (LSK(low)) is restricted by p18(INK4c).

    Science.gov (United States)

    Dong, Fang; Hao, Sha; Ma, Shihui; Cheng, Hui; Wang, Yajie; Zhou, Wen; Yuan, Weiping; Ema, Hideo; Cheng, Tao

    2016-09-01

    The cyclin-dependent kinase inhibitor CDKN2C (p18(INK4c)) restrains self-renewal in hematopoietic stem cells (HSCs) and participates in the development and maturation of lymphoid cells. Deficiency in p18 predisposes mice and humans to hematopoietic lymphoid malignancies such as T-cell leukemia and multiple myeloma. However, the mechanism by which p18 regulates differentiation from HSCs to lymphoid cells is poorly understood. In this study, we found that a progenitor population characterized by its expression of surface markers, Lin(-) Sca-1(+) c-Kit(low) (LSK(low)), was markedly expanded in the bone marrow of p18 knock-out (p18(-/-)) mice. This novel population possessed lymphoid differentiation potential, but not myeloid differentiation potential, both in vitro and in vivo. Whereas LSK(low) cells and common lymphoid progenitors (CLPs) overlapped functionally in generating lymphoid cells, they were distinct cell populations, because they had different gene expression profiles. Unlike CLPs, LSK(low) cells did not express the interleukin-7 receptor. LSK(low) cells were derived from HSCs and were independent of the p18-deleted microenvironment. This cell population may represent a previously unappreciated transitional stage from HSCs to lymphoid progenitors that is strictly restricted by p18 under physiological conditions. Likewise, LSK(low) might serve as a new cellular target of lymphoid malignances in the absence of p18.

  13. Genetic and epigenetic aberrations of p16 in feline primary neoplastic diseases and tumor cell lines of lymphoid and non-lymphoid origins.

    Science.gov (United States)

    Mochizuki, H; Fujiwara-Igarashi, A; Sato, M; Goto-Koshino, Y; Ohno, K; Tsujimoto, H

    2017-01-01

    The p16 gene acts as a tumor suppressor by regulating the cell cycle and is frequently inactivated in human and canine cancers. The aim of this study was to characterize genetic and epigenetic alterations of the p16 in feline lymphoid and non-lymphoid malignancies, using 74 primary tumors and 11 tumor cell lines. Cloning of feline p16 and subsequent sequence analysis revealed 11 germline sequence polymorphisms in control cats. Bisulfite sequencing analysis of the p16 promoter region in a feline lymphoma cell line revealed that promoter methylation was associated with decreased mRNA expression. Treatment with a demethylating agent restored mRNA expression of the silenced p16. PCR amplification and sequencing analysis detected homozygous loss (five tumors, 6.7%) and a missense mutation (one tumor, 1.4%) in the 74 primary tumors analyzed. Methylation-specific PCR analysis revealed promoter methylation in 10 primary tumors (14%). Promoter methylation was frequent in B cell lymphoid tumors (7/21 tumors, 33%). These genetic and epigenetic alterations were also observed in lymphoma and mammary gland carcinoma cell lines, but not detected in non-neoplastic control specimens. These data indicate that molecular alterations of the p16 locus may be involved in the development of specific types of feline cancer, and warrant further studies to evaluate the clinical value of this evolutionarily-conserved molecular alteration in feline cancers.

  14. Inclusion bodies and hepatopathies in psittacines.

    Science.gov (United States)

    Pass, D A

    1987-01-01

    Intranuclear inclusion bodies in hepatic cells of seven Peach-faced Lovebirds (Agapornis roseicollis), two Black-masked Love birds (A. personata) and two galahs (Cacatua roseicapilla) were examined electron microscopically. Thin sections were prepared from formalin-fixed Epon-embedded tissue or from haematoxylin and eosin stained sections that were subsequently embedded in Epon. Discrete and diffuse eosinophilic inclusions in hepatocytes of eight birds were composed of filaments and virus particles were not demonstrated within them. Virus-like particles of at least three types were found in diffuse, lightly basophilic inclusions of similar appearance in hepatocytes and Kupffer cells or endothelial cells in four birds. Particles, 66 nm in diameter which were probably adenovirus were demonstrated in hepatocytes in one A. roseicollis. Particles 26 nm to 39 nm in diameter which resembled papovaviruses were seen in one A. personata and one C. roseicapilla. Particles of 40 nm to 50 nm in diameter were seen in one A. personata but because of the method of preparation it was not possible to state whether they were adenovirus or papovavirus.

  15. The effect of cyclosporine, total lymphoid irradiation, and cobra venom factor on hyperacute rejection.

    Science.gov (United States)

    Knechtle, S J; Halperin, E C; Murphy, C E; Saad, T; Abernethy, K; Miller, D; Bollinger, R R

    1985-01-01

    Transplantation into sensitized recipients is contraindicated due to the potential for hyperacute rejection. In order to study the mechanism of hyperacute rejection and the role of immunosuppression in the face of presensitization, we evaluated the effect of total lymphoid irradiation, cyclosporine, and cobra venom factor, alone and in combination, on hyperacute rejection of heterotopic rat heart allografts. Lewis rats were sensitized to strongly RT-1-incompatible ACI rats by three successive skin grafts. Heart allografts were then performed, and survived for a mean period of 15.7 +/- 7.4 hours. Neither preoperative treatment of hypersensitized rats with total lymphoid irradiation alone nor with cyclosporine (5 mg/kg/day) resulted in a prolongation of survival (20.4 +/- 16.6 hours and 35.6 +/- 6.2 hours, respectively). However, complement depletion using cobra venom factor significantly prolonged mean graft survival time to 114.4 +/- 31.0 hours (p less than 0.05). Cyclosporine (10 mg/kg/day) also significantly prolonged survival to 149 +/- 29 hours (p less than 0.01), but did not lower the antibody or complement levels. The addition of total lymphoid irradiation or cyclosporine to treatment with cobra venom factor did not result in longer survival than cobra venom factor alone. In conclusion, cobra venom factor and cyclosporine delay but do not prevent hyperacute rejection, while total lymphoid irradiation has no observable effect on hyperacute rejection.

  16. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...

  17. Another armament in gut immunity: lymphotoxin-mediated crosstalk between innate lymphoid and dendritic cells.

    Science.gov (United States)

    Spits, H

    2011-07-21

    Innate lymphoid cells (ILCs) are novel players in innate immunity. Tumanov et al. (Tumanov et al., 2011) demonstrate that crosstalk between ILCs and dendritic cells involving membrane-bound lymphotoxin in ILCs and its receptor is critical for protection against colitogenic bacteria.

  18. Ultrasound Findings of Lymphoid Hyperplasia of the Appendix in Children: Differentiation from Acute Appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bong Jae; Seo, Jung Wook; Lee, Byung Hoon [Inje University Ilsan Paik Hospital, Koyang (Korea, Republic of)

    2009-12-15

    To evaluate the ultrasound (US) findings that can help differentiate lymphoid hyperplasia in the appendix from acute appendicitis. A total of 1230 patients (below 20 years old) suspected of having appendicitis received an appendectomy between November, 1999, and March, 2008, with US findings in 27 patients with pathologically proven lymphoid hyperplasia of the appendix. Of 167 patients that received an appendectomy from January, 2007, to December, 2007, 52 patients with acute appendicitis were retrospectively reviewed as a control group. Retrospective review of US images was performed by two radiologists who were blinded to the pathologic results. The review was based on 12 ultrasonographic criteria derived from reports on the diagnostic findings of the appendicitis. Compared with acute appendicitis, lymphoid hyperplasia in appendix had a smaller diameter (7.14{+-}1.22 mm vs 9.37{+-}1.80 mm, p < 0.001) and less wall thickening(1.38{+-}0.36 mm vs 1.74 {+-} 0.56 mm, p =0.001). Periappendicular inflammation (p < 0.001), intraluminal air (p = 0.006), round shape in transverse scan (p = 0.002),increased blood flow on color Doppler US (p = 0.03) were also different. US is a useful modality to differentiate lymphoid hyperplasia in the appendix from acute appendicitis

  19. Genotypic and phenotypic aspects of primary immunodeficiency diseases of the lymphoid system

    NARCIS (Netherlands)

    J.G. Noordzij

    2002-01-01

    textabstractThis thesis focuses on the immunological phenotype, the mutation analysis, and the residual activity of mutated proteins in patients with PID of the lymphoid system. During this project, we have investigated possible genotype-(immuno)phenotype relationships in patients with antibody defi

  20. Total lymphoid irradiation in heart transplantation: Adjunctive treatment for recurrent rejection

    Energy Technology Data Exchange (ETDEWEB)

    Frist, W.H.; Winterland, A.W.; Gerhardt, E.B.; Merrill, W.H.; Atkinson, J.B.; Eastburn, T.E.; Stewart, J.R.; Eisert, D.R. (Vanderbilt Univ. Medical Center, Nashville, TN (USA))

    1989-12-01

    In the face of recurrent heart transplant graft rejection refractory to all conventional immunotherapy, retransplantation is customary treatment. The case of a heart transplant recipient unsuitable for retransplantation whose recurrent rejection was successfully treated with postoperative total lymphoid irradiation is described.

  1. Another Armament in Gut Immunity: Lymphotoxin-Mediated Crosstalk between Innate Lymphoid and Dendritic Cells

    NARCIS (Netherlands)

    H. Spits

    2011-01-01

    Innate lymphoid cells (ILCs) are novel players in innate immunity. Tumanov et al. (Tumanov et al., 2011) demonstrate that crosstalk between ILCs and dendritic cells involving membrane-bound lymphotoxin in ILCs and its receptor is critical for protection against colitogenic bacteria

  2. Identifying therapeutic targets by elucidating signaling pathways in pediatric lymphoid leukemias

    NARCIS (Netherlands)

    van der Sligte, Naomi Eline

    2015-01-01

    Despite intensive chemotherapy, acute lymphoblastic leukemia (ALL) relapse is still a major cause of cancer-related death in children and the survival of children with lymphoid blast crisis chronic myeloid leukemia (CML-LyBC) is even worse. Further improvements in outcome, achieved by dose optimizat

  3. The promising impact of ibrutinib, a Bruton's tyrosine kinase inhibitor, for the management of lymphoid malignancies.

    Science.gov (United States)

    Bhatt, Valkal; Alejandro, Linh; Michael, Angela; Ganetsky, Alex

    2014-03-01

    Lymphoid malignancies comprise a heterogeneous group of disorders originating from clonal proliferation of B or T lymphocytes. Treatment of lymphoid neoplasms has traditionally been pursued with cytotoxic chemotherapy. To improve efficacy and ameliorate the adverse effects associated with classic chemotherapy, molecularly targeted therapy has been developed. At the forefront of clinical development is ibrutinib, an inhibitor of Bruton's tyrosine kinase (Btk). Btk is a protein tyrosine kinase that plays an important role in regulating B-cell signaling. Dysregulated Btk results in uncontrolled B-lymphocyte proliferation, differentiation, and survival. Ibrutinib is currently being studied in numerous malignancies of lymphoid origin including chronic lymphocytic leukemia, mantle cell lymphoma, non-Hodgkin lymphoma, follicular lymphoma, and multiple myeloma. Thus far, ibrutinib has demonstrated very promising results in treatment-naive patients as well as those with relapsed or refractory disease with an acceptable safety profile. In this article, we describe the pharmacology, efficacy, and toxicity profile of ibrutinib and depict the potential role that ibrutinib will play in the treatment paradigm of lymphoid neoplasms. © 2013 American College of Clinical Pharmacy.

  4. Treatment of severe aplastic anaemia with total lymphoid irradiation and methylprednisolone

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, J.; Singhal, S. (Blood Research Centre, Bombay (India)); Huilgol, N.; Merchant, R.; Mehta, B.C. (Nanavati Hospital and Research Centre, Bombay (India))

    1992-05-01

    This case report briefly summarizes the treatment of aplastic anaemia with total lymphoid irradiation and methylprednisolone and recommends that this procedure should be considered a therapeutic option in patients who are not candidates for bone marrow transplantation or antithymocyte globulin, or those who have failed one course of the latter. (Author).

  5. NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2015-03-01

    Full Text Available Innate lymphoid cells (ILCs are a family of effectors that originate from a common innate lymphoid cell progenitor. However, the transcriptional program that sets the identity of the ILC lineage remains elusive. Here, we show that NFIL3 is a critical regulator of the common helper-like innate lymphoid cell progenitor (CHILP. Cell-intrinsic Nfil3 ablation led to variably impaired development of fetal and adult ILC subsets. Conditional gene targeting demonstrated that NFIL3 exerted its function prior to ILC subset commitment. Accordingly, NFIL3 ablation resulted in loss of ID2+ CHILP and PLZF+ ILC progenitors. Nfil3 expression in lymphoid progenitors was under the control of the mesenchyme-derived hematopoietin IL-7, and NFIL3 exerted its function via direct Id2 regulation in the CHILP. Moreover, ectopic Id2 expression in Nfil3-null precursors rescued defective ILC lineage development in vivo. Our data establish NFIL3 as a key regulator of common helper-like ILC progenitors as they emerge during early lymphopoiesis.

  6. Body size in early life and risk of lymphoid malignancies and histological subtypes in adulthood.

    Science.gov (United States)

    Yang, TienYu Owen; Cairns, Benjamin J; Kroll, Mary E; Reeves, Gillian K; Green, Jane; Beral, Valerie

    2016-07-01

    Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17-1.51, for BMI 35+ vs <22.5 kg/m(2)), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10-1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small.

  7. Tertiary lymphoid structures are confined to patients presenting with unifocal Langerhans Cell Histiocytosis.

    Science.gov (United States)

    Quispel, Willemijn T; Steenwijk, Eline C; van Unen, Vincent; Santos, Susy J; Koens, Lianne; Mebius, Reina; Egeler, R Maarten; van Halteren, Astrid G S

    2016-08-01

    Langerhans cell histiocytosis (LCH) is a neoplastic myeloid disorder with a thus far poorly understood immune component. Tertiary lymphoid structures (TLS) are lymph node-like entities which create an immune-promoting microenvironment at tumor sites. We analyzed the presence and clinical relevance of TLS in n = 104 H&E-stained, therapy-naive LCH lesions of non-lymphoid origin and applied immunohistochemistry to a smaller series. Lymphoid-follicular aggregates were detected in 34/104 (33%) lesions. In line with the lymphocyte recruitment capacity of MECA-79(+) high endothelial venules (HEVs), MECA-79(+)-expressing-LCH lesions (37/77, 48%) contained the most CD3(+) T-lymphocytes (p = 0.003). TLS were identified in 8/15 lesions and contained T-and B-lymphocytes, Follicular Dendritic Cells (FDC), HEVs and the chemokines CXCL13 and CCL21 representing key cellular components and TLS-inducing factors in conventional lymph nodes (LN). Lymphoid-follicular aggregates were most frequently detected in patients presenting with unifocal LCH (24/70, 34%) as compared to patients with poly-ostotic or multi-system LCH (7/30, 23%, p = 0.03). In addition, patients with lymphoid-follicular aggregates-containing lesions had the lowest risk to develop new LCH lesions (p = 0.04). The identification of various stages of TLS formation within LCH lesions may indicate a key role for the immune system in controlling aberrant histiocytes which arise in peripheral tissues.

  8. Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies

    Science.gov (United States)

    Anderson, Lesley A; Gadalla, Shahinaz; Morton, Lindsay M; Landgren, Ola; Pfeiffer, Ruth; Warren, Joan L; Berndt, Sonja I; Ricker, Winnie; Parsons, Ruth; Engels, Eric A

    2008-01-01

    Some autoimmune conditions are associated with increased risk of lymphoid malignancies, but information on specific malignancy subtypes is limited. From the U.S. Surveillance Epidemiology and End Results-Medicare database, we selected 44,350 lymphoid malignancy cases (≥67 years) and 122,531 population-based controls. Logistic regression was used to derive odds ratios (ORs) comparing the prevalence of autoimmune conditions in cases and controls, by lymphoid malignancy subtype, adjusted for gender, age at malignancy/selection, year of malignancy/selection, race and number of physician claims. The strongest associations observed by Non-Hodgkin lymphoma (NHL) subtypes were diffuse large B-cell lymphoma with rheumatoid arthritis (OR 1.4, 95%CI 1.2-1.5) and Sjögren syndrome (2.0, 1.5-2.8); T-cell lymphoma with hemolytic anemia (9.7, 4.3-22), psoriasis (3.1, 2.5-4.0), discoid lupus erythematosus (4.4, 2.3-8.4), and celiac disease (5.0, 2.4-14.); and marginal zone lymphoma with Sjögren syndrome (6.6, 4.6-9.5), systemic lupus erythematosus (2.8, 1.7-4.7), and hemolytic anemia (7.4, 3.1-18). Hodgkin lymphoma was associated with several autoimmune conditions. Multiple myeloma was associated only with pernicious anemia (1.5, 1.3-1.7). Several autoimmune conditions were associated with increased risk of lymphoid neoplasms, especially NHLs of diffuse large B-cell, marginal zone and T-cell subtypes. These results support a mechanism whereby chronic antigenic stimulation leads to lymphoid malignancy. PMID:19365835

  9. Spinal Cord Ventral Horns and Lymphoid Organ Involvement in Powassan Virus Infection in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Rodrigo I. Santos

    2016-08-01

    Full Text Available Powassan virus (POWV belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investigate POWV infection and pathogenesis. After footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. Immunohistochemistry and immunofluorescence revealed a very strong neuronal tropism of POWV infection. The central nervous system infection appeared as a meningoencephalitis with perivascular mononuclear infiltration and microglial activation in the brain, and a poliomyelitis-like syndrome with high level of POWV antigen at the ventral horn of the spinal cord. Pathological studies also revealed substantial infection of splenic macrophages by POWV, which suggests that the spleen plays a more important role in pathogenesis than previously realized. This report provides a detailed description of the neuroanatomical distribution of the lesions produced by POWV infection in C57BL/6 mice.

  10. IFN-α Is Constitutively Expressed in the Human Thymus, but Not in Peripheral Lymphoid Organs

    NARCIS (Netherlands)

    Colantonio, A.D.; Epeldegui, M.; Jesiak, M.; Jachimowski, L.; Blom, B.; Uittenbogaart, C.H.

    2011-01-01

    Type I interferons have been typically studied for their effects in the context of bacterial or viral infections. However in this report, we provide evidence that Interferon-alpha (IFN-α) expressing cells are present in the thymus in the absence of infection. We show that pDC express the highest

  11. Multispectral imaging reveals the tissue distribution of tetraspanins in human lymphoid organs

    NARCIS (Netherlands)

    Winde, C.M. de; Zuidscherwoude, M.C.; Vasaturo, A.; Schaaf, A. van der; Figdor, C.G.; Spriel, A.B. van

    2015-01-01

    Multispectral imaging is a novel microscopy technique that combines imaging with spectroscopy to obtain both quantitative expression data and tissue distribution of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane proteins involved in cellular and humoral immune response

  12. Estren promotes androgen phenotypes in primary lymphoid organs and submandibular glands

    Directory of Open Access Journals (Sweden)

    Gustafsson Jan-Åke

    2005-07-01

    Full Text Available Abstract Background Estrogens and androgens have extensive effects on the immune system, for example they suppress both T and B lymphopoiesis in thymus and bone marrow. Submandibular glands are sexually dimorphic in rodents, resulting in larger granular convoluted tubules in males compared to females. The aim of the present experiments was to investigate the estrogenic and androgenic effects of 4-estren-3α,17β-diol (estren on thymus, bone marrow and submandibular glands, and compare the effects to those of 17β-estradiol (E2 and 5α-dihydrotestosterone (DHT, respectively. Estrogen receptors (ERs were blocked by treatment of mice with the ER-antagonist ICI 182,780; also, knock-out mice lacking one or both ERs were used. Results As expected, the presence of functional ERs was mandatory for all the effects of E2. Similar to DHT-treatment, estren-treatment resulted in decreased thymus weight, as well as decreased frequency of bone marrow B cells. Treatment with estren or DHT also resulted in a shift in submandibular glands towards an androgen phenotype. All the effects of estren and DHT were independent of ERs. Conclusion Our study is the first to show that estren has similar effects as the androgen DHT on lymphopoiesis in thymus and bone marrow, and on submandibular glands, and that these effects are independent of estrogen receptors. This supports the hypothesis of estren being able to signal through the androgen receptor.

  13. IFN-α Is Constitutively Expressed in the Human Thymus, but Not in Peripheral Lymphoid Organs

    NARCIS (Netherlands)

    Colantonio, A.D.; Epeldegui, M.; Jesiak, M.; Jachimowski, L.; Blom, B.; Uittenbogaart, C.H.

    2011-01-01

    Type I interferons have been typically studied for their effects in the context of bacterial or viral infections. However in this report, we provide evidence that Interferon-alpha (IFN-α) expressing cells are present in the thymus in the absence of infection. We show that pDC express the highest lev

  14. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    Science.gov (United States)

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life.

  15. [Comparative characteristics of cellular composition of the lymphoid structure of various regions of the human intestine in early childhood].

    Science.gov (United States)

    Aminova, G G; Grigorenko, D E; Rusina, A K

    1997-01-01

    Using microscopic methods and statistic analysis lymphoid structures of large and small intestine walls and appendix were studied in 4-7 years children. The highest cell reproductive activity was detected in duodenal walls being slightly lower in appendix and group lymphoid vessels. The highest ratio of plasma cells was found in duodenum, ileal lymphoid patches and cecum, where the index was 7-fold higher than index of appendix and ileum. Lamina propria of intestinal mucosa is characterized by small fraction of mitotically dividing cells and undifferentiated cell forms, especially in cecum walls. However, the latter shows the greatest percentage of plasma cells.

  16. Blood myeloid and lymphoid dendritic cells reflect Th1/Th2 balance in sarcoidosis and extrinsic allergic alveolitis.

    Science.gov (United States)

    Buczkowski, Jarosław; Krawczyk, Paweł; Chocholska, Sylwia; Tabarkiewicz, Jacek; Kieszko, Robert; Michnar, Marek; Milanowski, Janusz; Roliński, Jacek

    2003-01-01

    Dendritic cells play a specific regulatory role in the immune system. In this paper, the significance of myeloid and lymphoid dendritic cells in sarcoidosis and extrinsic allergic alveolitis (EAA) was evaluated. Myeloid dendritic cells are connected with Th1 type of immunological response, whereas lymphoid ones--with Th2 type. The latest findings indicate that both diseases are characterized by serious disturbances of Th1/Th2 response to Th1 dominance. Our studies seem to confirm these suggestions. In the peripheral blood of patients with sarcoidosis as well as with EAA, myeloid dendritic cells outnumbered lymphoid ones.

  17. Growth performance, immune status and organ morphometry in ...

    African Journals Online (AJOL)

    Growth performance, immune status and organ morphometry in broilers fed Bacillus subtilis ... South African Journal of Animal Science ... The present research aimed to investigate the effects of Bacillus subtilis (B. subtilis) on performance, immune system, gut, and lymphoid organs' microarchitecture in broilers. A total of ...

  18. Influence of age, sex and rearing systems on Toll-like receptor 7 (TLR7) expression pattern in gut, lung and lymphoid tissues of indigenous ducks.

    Science.gov (United States)

    Kolluri, Gautham; Ramamurthy, N; Churchil, R R; Dhinakar Raj, G; Kannaki, T R

    2014-02-01

    Abstract 1. The objective of the experiment was to determine the influence of age, sex and rearing system on Toll-like receptor 7 (TLR7) gene expression in gut, lung and lymphoid tissues and physiological responses to stress in male and female indigenous ducks of Tamil Nadu, India. 2. A total of 36 ducks (12 males and 24 females) were obtained from local farmers and tissue samples of gut tissues (duodenum, jejunum, ileum and caecum), lymphoid organs (spleen and bursa) and lungs were collected in RNAlater solution followed by RNA extraction. 3. After normalisation to β-actin (endogenous control) qPCR analysis identified a significant effect of age, sex and rearing system on TLR7 expression in the ducks. 4. A significant up-regulation of TLR7 expression was observed in lungs, duodenum, jejunum, ileum and caecum of sexually mature (45 wk) compared with that of immature ducks (16 wk). Among sexes, male ducks had significantly higher TLR7 expression than female ducks. 5. Age and sex interactions were significant in lungs, duodenum, jejunum and caecum. Ducks reared in an extensive housing system showed significantly higher TLR7 expression in bursa, lungs, duodenum, ileum and caecum compared to intensively reared ducks. There were no effects of age, sex and rearing systems on TLR7 expression in the spleen. 6. The heterophil-to-lymphocyte ratio and serum corticosterone were higher in ducks reared on an intensive system compared with ducks from an extensive rearing system.

  19. Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection.

    Science.gov (United States)

    Yang, L; Yamamoto, K; Nishiumi, S; Nakamura, M; Matsui, H; Takahashi, S; Dohi, T; Okada, T; Kakimoto, K; Hoshi, N; Yoshida, M; Azuma, T

    2015-03-01

    Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.

  20. Pseudolymphoma (reactive lymphoid hyperplasia) of the liver:A clinical challenge

    Institute of Scientific and Technical Information of China (English)

    Yong; Kyong; Kwon; Reena; C; Jha; Kambiz; Etesami; Thomas; M; Fishbein; Metin; Ozdemirli; Chirag; S; Desai

    2015-01-01

    Reactive lymphoid hyperplasia(RLH), also known as pseudolymphoma or nodular lymphoid lesion of the liver is an extremely rare condition, and only 51 hepatic RLH cases have been described in the literature since the first case was described in 1981. The majority of these cases were asymptomatic and incidentally found through radiological imaging. The precise etiology of hepatic RLH is still unknown, but relative high prevalence of autoimmune disorder in these cases suggests an immune-based liver disorder. Imaging features of hepatic RLH often suggest malignant lesions such as hepatocellular carcinoma and cholangiocarcinoma. In this report, we discuss two cases of hepatic RLH in patients with autoimmune hepatitis. We also present pathologic and magnetic resonance imaging findings, including one case utilizing a hepatocellular contrast agent, Eovist. Definitive diagnosis of hepatic RLH often requires surgical excision.

  1. 蛋鸡淋巴白血病的诊断%Diagnosis of Avian Lymphoid Leukosis

    Institute of Scientific and Technical Information of China (English)

    刘金霞

    2012-01-01

    2011年某蛋鸡场部分病鸡内脏发生增生性肿瘤性疾病,经流行病学调查、临床诊断及实验室检测,确诊为鸡J亚型淋巴白血病.文章就该病例的诊断过程做了详细阐述,并对禽常见传染性肿瘤病的鉴别、白血病的预防和控制进行了归纳总结.%Some suspected avian lekosis samples were got from one chicken farm in Tongzhou. After epidemiological survey, clinical diagnosis and experiment detection, confirmed diagnosis conclusion was lymphoid leukosis. This article mainly e-laborated the diagosis process of the case and summarized the identification, prevention and control measure of lymphoid leukosis.

  2. Staining of Langerhans Cells with Monoclonal Antibodies to Macrophages and Lymphoid Cells

    Science.gov (United States)

    Haines, Kathleen A.; Flotte, Thomas J.; Springer, Timothy A.; Gigli, Irma; Thorbecke, G. Jeanette

    1983-06-01

    Langerhans cells are Ia-bearing antigen-presenting cells in the epidermis that share many functions with macrophages. We have used monoclonal antibodies to the macrophage antigens, Mac-2 and -3, Ia antigen, Fc fragment receptor, and the common leukocyte antigen CLA to compare the cell surface antigens of these cells with those of interdigitating and follicular dendritic cells and of macrophages in lymphoid tissues. Immunoperoxidase staining was carried out with epidermal sheets from BALB/c mice and epidermal cell suspensions enriched for Langerhans cells by Fc rosetting. Langerhans cells stained for all of these antigens. Comparison with the staining properties of other dendritic cells and macrophages, in combination with previous observations, indicates a close relationship of Langerhans cells to the interdigitating cells of lymphoid tissues.

  3. Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn; Vetter-Kauczok, Claudia S; Woetmann, Anders;

    2009-01-01

    B-lymphoid kinase (Blk) is exclusively expressed in B cells and thymocytes. Interestingly, transgenic expression of a constitutively active form of Blk in the T-cell lineage of mice results in the development of T-lymphoid lymphomas. Here, we demonstrate nuclear factor-kappa B (NF......-kappaB)-mediated ectopic expression of Blk in malignant T-cell lines established from patients with cutaneous T-cell lymphoma (CTCL). Importantly, Blk is also expressed in situ in lesional tissue specimens from 26 of 31 patients with CTCL. Already in early disease the majority of epidermotropic T cells express Blk...... phosphorylated in malignant CTCL cell lines and spontaneously active in kinase assays. Furthermore, targeting Blk activity and expression by Src kinase inhibitors and small interfering RNA (siRNA) inhibit the proliferation of the malignant T cells. In conclusion, this is the first report of Blk expression...

  4. Cytokine receptor expression in human lymphoid tissue: analysis by fluorescence microscopy.

    Science.gov (United States)

    Zola, H; Ridings, J; Weedon, H; Fusco, M; Byard, R W; Macardle, P J

    1995-08-01

    A highly-sensitive flourescence method, capable of detecting cytokine receptors present at low concentrations (around 100 molecules per cell) by flow cytometry, was adapted for use on tissue sections. This method was used to examine the expression of several cytokine receptors in lymphoid tissues. IL-2 receptors were distributed broadly, with higher concentrations in T cell areas. IL-1 receptor Type 1 was detected in T cell areas and in the follicular mantle, and was strongly expressed on vascular endothelium. IL-6 receptor was found at very low concentration, both within and outside germinal centres. The gp 130 molecule, which is involved in the functional receptor complex for IL-6 and several other cytokines, was present at higher concentrations, particularly in the germinal centre. Analysis of receptor expression in secondary lymphoid tissue provides evidence bearing on the physiological roles of cytokines, as these tissues contain cells at various stages of physiological activation located in well-defined functional zones.

  5. Herpesvirus infection with severe lymphoid necrosis affecting a beaked whale stranded in the Canary Islands.

    Science.gov (United States)

    Arbelo, Manuel; Sierra, Eva; Esperón, Fernando; Watanabe, Tatiane T N; Bellière, Edwige N; Espinosa de los Monteros, Antonio; Fernández, Antonio

    2010-04-01

    This report describes the pathologic findings in a single, adult female Cuvier's beaked whale Ziphius cavirostris stranded in the Canary Islands. The study indicated that this whale died with a severe, systemic, herpesviral infection and clearly exhibited lesions different from those of the fat and gas embolic syndrome described in beaked whale mass strandings associated with sonar exposure. This is the first report of a cetacean alphaherpesvirus infection of the lymphoid system in a beaked whale.

  6. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system

    Directory of Open Access Journals (Sweden)

    Enrique Montalvillo

    2014-05-01

    Full Text Available The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity. Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  7. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system.

    Science.gov (United States)

    Montalvillo, Enrique; Garrote, José Antonio; Bernardo, David; Arranz, Eduardo

    2014-05-01

    The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity.Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  8. Lymphoid associated antigen expression in new cases of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    R Jha

    2013-10-01

    Full Text Available Background: Occurrence of aberrant phenotype has been reported in acute leukemias with varying frequency though its prognostic importance remains controversial. In acute myeloid leukemias, aberrant phenotype, as high as 88 %, has been reported. To evaluate the occurrence of aberrant lymphoid phenotypes and to correlate their presence with various French American British classification, 100 cases of fresh acute myeloid leukemias were analyzed for lymphoid markers CD 4,7,8,10 and 19. Materials and Methods: Whole blood or bone marrow aspirate collected in EDTA were processed by standard method and subjected to immunophenotyping for B Cells marker CD 19 and 10 and T cell marker CD 4, 7 and 8. Results: Aberrant lymphoid markers were seen in 35(35% cases. All FAB subtypes except M7 showed aberrancy for the markers studied. However it was the most common in M0 (100%, followed by M2 (51.9%. T cell aberrancy was the most common, comprising 62.8% (22/35 of total aberrancy. CD 7 was the most common aberrantly expressed marker, seen in 20% AML, followed by CD 4(14% and CD 19 (8%. Conclusion: Occurrence of lymphoid phenotypes is frequent in pediatric as well adult AML. Though T cell markers are more common, only B cell as well as both B and T cell markers may be co expressed. DOI: http://dx.doi.org/10.3126/jpn.v3i6.8999   Journal of Pathology of Nepal (2013 Vol. 3, 487-490

  9. Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells☆

    OpenAIRE

    Fazal, Nadeem; Shelip, Alla; Alzahrani, Alhusain J.

    2013-01-01

    After scald burn-injury, the intestinal immune system responds to maintain immune balance. In this regard CD4+T cells in Gut-Associated Lymphoid Tissues (GALT), like mesenteric lymph nodes (MLN) and Peyer's patches (PP) respond to avoid immune suppression following major injury such as burn. Therefore, we hypothesized that the gut CD4+T cells become dysfunctional and turn the immune homeostasis towards depression of CD4+ T cell-mediated adaptive immune responses. In the current study we show ...

  10. Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency

    Science.gov (United States)

    Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J.; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M.; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte

    2016-01-01

    Background Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Objectives Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Methods Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. Results The linage-negative, CD127+, CD161+ lymphoid population containing T-box transcription factor, retinoic acid–related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ+RORγt+CD3− cells were identified, suggesting a role in these mucosal inflammatory states. Conclusions An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. PMID:26542033

  11. A case of colonic lymphoid tissue invasion by Gymnophalloides seoi in a Korean man

    OpenAIRE

    Seo, Min; Chun, Hokyung; Ahn, Geunghwan; Jang, Kee-Taek; Guk, Sang-Mee; Chai, Jong-Yil

    2006-01-01

    A 65-year old Korean man, living in Mokpo-city, Jeollanam-do, Republic of Korea, visited a local clinic complaining of right upper quadrant pain and indigestion. At colonoscopy, he was diagnosed as having a carcinoma of the ascending colon, and thus, a palliative right hemicolectomy was performed. Subsequently, an adult fluke of Gymnophalloides seoi was incidentally found in a surgical pathology specimen of the lymph node around the colon. The worm was found to have invaded gut lymphoid tissu...

  12. Venous thromboembolism following L-asparaginase treatment for lymphoid malignancies in Korea.

    Science.gov (United States)

    Lee, J H; Lee, J; Yhim, H-Y; Oh, D; Bang, S-M

    2017-02-02

    Essentials Data on venous thromboembolism (VTE) after L-asparaginase (L-asp) in Asian lymphoma are scarce. This is a population-based study in Asian patients with lymphoid disease and L-asp-related VTE. The overall incidence of L-asp-associated VTE was similar to reports on Caucasians. This first and largest study in Asians shows that mainly adult patients are at risk of thrombosis.

  13. In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

    Science.gov (United States)

    Lew, Y Y; Michalak, T I

    2001-02-01

    Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

  14. Optimization of retroviral gene transfer protocol to maintain the lymphoid potential of progenitor cells.

    Science.gov (United States)

    Hacein-Bey, S; Gross, F; Nusbaum, P; Hue, C; Hamel, Y; Fischer, A; Cavazzana-Calvo, M

    2001-02-10

    We have attempted to improve retrovirus-mediated gene transfer efficacy into hematopoietic progenitor cells (HPCs) without causing them to lose their lymphoid potential. Highly purified CD34(+) cells on CH-296 fibronectin fragments have been transduced with three different cytokine combinations. Murine CD2 was used as a marker gene. Transgene expression was assayed by FACS analysis shortly after transduction of CD34(+) cells and after long-term culture (LTC) extended by differentiation of various lymphoid lineages: NK cells, B cells, and dendritic cells. Compared with the historical cytokine mix, i.e., SCF (stem cell factor) + IL-3 (interleukin 3) + IL-6, the combination SCF + FL (Flt-3 ligand) + M-GDF (megakaryocyte growth and differentiation factor) + IL-3 significantly improved the total number of viable cells and CD34(+) cells after transduction and the long term-cultured progenitors after 6 weeks. In addition, the combination of SCF + FL + M-GDF + IL-3 maintained more efficiently the lymphoid potential of the progeny of transduced long term-cultured CD34(+) cells, as attested by the significantly higher number of CD56(+), CD19(+), and CD1a(+) cells recovered when FL and M-GDF were added to SCF + IL-3. Thus, even though additional improvements may still be needed in transduction of HPCs, these conditions were adopted for a clinical trial of gene therapy for X-linked severe combined immunodeficiency.

  15. Common-Lymphoid-Progenitor-Independent Pathways of Innate and T Lymphocyte Development

    Directory of Open Access Journals (Sweden)

    Maryam Ghaedi

    2016-04-01

    Full Text Available All lymphocytes are thought to develop from common lymphoid progenitors (CLPs. However, lymphoid-primed multipotent progenitors (LMPPs are more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s. Here, we have divided LMPPs into CD127− (LMPP−s and CD127+ (LMPP+s subsets and compared them with Ly6D− and Ly6D+ CLPs. Adult LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. The development of T cells and ILC2s is highly active in the neonatal period. Neonatal CLPs are rare and, unlike prominent neonatal LMPP+s, do not efficiently differentiate into T cells and ILC2s. ILC2s generated in the neonatal period are long lived and persist in adult tissues. These results suggest that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways.

  16. Vascular Endothelial Growth Factor-Related Pathways in Hemato-Lymphoid Malignancies

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    Michael Medinger

    2010-01-01

    Full Text Available Angiogenesis is essential for malignant tumor growth. This has been documented for solid tumors, and there is an emerging evidence suggesting that tumor progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation. The most important proangiogenic agent is vascular endothelial growth factor (VEGF, activating VEGF receptors 1 and 2. The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. Several antiangiogenic agents targeting VEGF-related pathways are also being utilized in clinical trials for the treatment of hemato-lymphoid malignancies, and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hemato-lymphoid malignancies and the translation of such basic findings into clinical studies.

  17. Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review

    Institute of Scientific and Technical Information of China (English)

    Andreia; Albuquerque

    2014-01-01

    Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine(more often), stomach, large intestine, or rectum. The patho-genesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immu-nodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infec-tion, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointes-tinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germi-nal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submu-cosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodu-lar lymphoid hyperplasia is a risk factor for both intes-tinal and, very rarely, extraintestinal lymphoma. Someauthors recommend surveillance, however, the duration and intervals are undefined.

  18. NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

    2016-01-01

    Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  19. Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kikushige, Yoshikane; Miyamoto, Toshihiro

    2015-11-01

    Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

  20. Rapid, Nonradioactive Detection of Clonal T-Cell Receptor Gene Rearrangements in Lymphoid Neoplasms

    Science.gov (United States)

    Bourguin, Anne; Tung, Rosann; Galili, Naomi; Sklar, Jeffrey

    1990-11-01

    Southern blot hybridization analysis of clonal antigen receptor gene rearrangements has proved to be a valuable adjunct to conventional methods for diagnosing lymphoid neoplasia. However, Southern blot analysis suffers from a number of technical disadvantages, including the time necessary to obtain results, the use of radioactivity, and the susceptibility of the method to various artifacts. We have investigated an alternative approach for assessing the clonality of antigen receptor gene rearrangements in lymphoid tissue biopsy specimens. This approach involves the amplification of rearranged γ T-cell receptor genes by the polymerase chain reaction and analysis of the polymerase chain reaction products by denaturing gradient gel electrophoresis. By use of this approach, clonal rearrangements from neoplastic lymphocytes constituting as little as 0.1-1% of the total cells in the tissue are detected as discrete bands in the denaturing gel after the gel is stained with ethidium bromide and viewed under ultraviolet light. In contrast, polyclonal rearrangements from reactive lymphocytes appear as a diffuse smear along the length of the gel. Our findings suggest that polymerase chain reaction combined with denaturing gradient gel electrophoresis may offer a rapid, nonradioactive, and sensitive alternative to Southern blot analysis for the diagnostic evaluation of lymphoid tissue biopsy specimens.

  1. Lymphoid lineage differentiation potential of mouse nuclear transfer embryonic stem cells.

    Science.gov (United States)

    Eslami-Arshaghi, Tarlan; Salehi, Mohammad; Soleimani, Masoud; Gholipourmalekabadi, Mazaher; Mossahebi-Mohammadi, Majid; Ardeshirylajimi, Abdolreza; Rajabi, Hoda

    2015-09-01

    Stem cells therapy is considered as an efficient strategy for the treatment of some diseases. Nevertheless, some obstacles such as probability of rejection by the immune system limit applications of this strategy. Therefore, several efforts have been made to overcome this among which using the induced pluripotent stem cells (iPSCs) and nuclear transfer embryonic stem cell (nt-ESCs) are the most efficient strategies. The objective of this study was to evaluate the differentiation potential of the nt-ESCs to lymphoid lineage in the presence of IL-7, IL-3, FLT3-ligand and TPO growth factors in vitro. To this end, the nt-ESCs cells were prepared and treated with aforementioned growth factors for 7 and 14 days. Then, the cells were examined for expression of lymphoid markers (CD3, CD25, CD127 and CD19) by quantitative PCR (q-PCR) and flow cytometry. An increased expression of CD19 and CD25 markers was observed in the treated cells compared with the negative control samples by day 7. After 14 days, the expression level of all the tested CD markers significantly increased in the treated groups in comparison with the control. The current study reveals the potential of the nt-ESCs in differentiation to lymphoid lineage in the presence of defined growth factors.

  2. CELLULAR LOCALIZATION OF IMMUNOGLOBULINS WITH DIFFERENT ALLOTYPIC SPECIFICITIES IN RABBIT LYMPHOID TISSUES

    Science.gov (United States)

    Pernis, Benvenuto; Chiappino, Gerolamo; Kelus, Andrew S.; Gell, Philip G. H.

    1965-01-01

    The cellular localization of allotypes in rabbit lymphoid tissues has been studied by immunofluorescence. In heterozygous animals the double staining for two allotypes controlled by allelic genes (A1 and A2; A4 and A5; A4 and A6) has shown the existence of two populations of plasma cells, one containing one allotype and the other the alternative one. The localization in different cells of immunoglobulins marked by allelic allotypic specificities has been confirmed by microspectrography of single cells. An exception to this rule was given by the presence in the germinal centers of lymphoid follicles of apparently uniform mixtures of products of the two allelic genes. Double staining for two allotypes controlled by genes at different loci showed, instead, the presence of many cells containing both allotypes; the number of these cells was highest in doubly homozygotes, in the other it was consistent with random association of non-allelic specificities. In addition double staining for one allotype and gamma G globulins in the lymphoid tissues of rabbits homozygous at the a or at the b locus, has shown the presence of cells containing immunoglobulins that lack one allotype. PMID:4159057

  3. Nodular lymphoid hyperplasia of the colon in a vervet monkey (Cholorocebous aethiops).

    Science.gov (United States)

    Hablolvarid, M H

    2014-12-01

    Diffuse nodular lymphoid hyperplasia (DNLH) of gastrointestinal tract is regarded as a very rare disease in the adult population. It is characterized by presence of diffuse detectable small polypoid masses distributed in the small intestine, colon, or both. A 6-year-old male in captivity suddenly died, due to myocardial infarction. During routine necropsy procedure, incidentally, numerous tan, sessile polyps, up to 0.2 cm were noticed in all segments of the colon. Histopathological and immunohistochemical examination revealed polypoid masses as nodular lymphoid hyperplasia (NLH), comparable with DNLH of the colon in human. In this article, the author has tried to introduce some immunosuppresive (e.g., simian retrovirus type D (SRV), simian immunodeficiency virus (SIV)) and opportunistic viruses (e.g., lymphocryptovirus, γ-herpesvirus, adenovirus), as well as, primary and opportunistic bacteria (e.g., Yersinia psedotuberculosis, and Helicobacter spp.) that may trigger benign reactive process, lymphoid hyperplasia, in non-human primates (NHPs) in captivity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. CD4+ lymphoid tissue inducer cells promote innate immunity in the gut

    Science.gov (United States)

    Sonnenberg, Gregory F.; Monticelli, Laurel A.; Elloso, M. Merle; Fouser, Lynette A.; Artis, David

    2010-01-01

    SUMMARY Fetal CD4+ lymphoid tissue inducer (LTi) cells play a critical role in the development of lymphoid-tissues. Recent studies identified that LTi cells persist in adults and are related to a heterogeneous population of innate lymphoid cells that have been implicated in inflammatory responses. However, whether LTi cells contribute to protective immunity remains poorly defined. We demonstrate that following infection with Citrobacter rodentium, CD4+ LTi cells were a dominant source of interleukin-22 (IL-22) early during infection. Infection-induced CD4+ LTi cell responses were IL-23-dependent, and ablation of IL-23 impaired innate immunity. Further, depletion of CD4+ LTi cells abrogated infection-induced expression of IL-22 and anti-microbial peptides, resulting in exacerbated host mortality. LTi cells were also found to be essential for host protective immunity in lymphocyte-replete hosts. Collectively these data demonstrate that adult CD4+ LTi cells are a critical source of IL-22 and identify a previously unrecognized function for CD4+ LTi cells in promoting innate immunity in the intestine. PMID:21194981

  5. Sexual peculiarities of lymphoid formations in trachea and bronchi of individuals of different age groups

    Directory of Open Access Journals (Sweden)

    V.B. Shadlinsky

    2010-03-01

    Full Text Available The aim of the investigation is to study the sexual peculiarities of lymphoid formations in trachea and bronchi of individuals of different age groups. The lymphoid apparatus of trachea and bronchi has been studied. taken from 58 humans of different age and both sexes, died or perished in accidents without pathologies of respiratory and immune systems was studied via microscopical methods. The trachea and bronchi principalis were fixated in 10% solution of formalin and in water Karnua. The longitudinal and transverse pieces were taken from cartilaginous and membranaceus walls of the upper, middle and lower one-third of the trachea and each bronchi principalis. These cuts 5-7 urn in thickness were stained with hematoxylin-eosin, azure-2-eosin, with hematoxylin-picrofucsin by Van-Gizon technique, with methyl green-pironin by Brashe technique (after fixation in water Karnua and reaction by Grymelius. The results of the research showed that during postnatal ontogenesis the sex related differences are observed in cell composition of the trachea and bronchi princiapalis' lymphoid structures. In adolescent, juvenile and 1-st mature period in females the percentage of small and big lymphocytes, cells with mitosis, plasma cells is more, but the percentage of medium lymphocytes and cells with degeneration is less than in males

  6. Relationship of lymphoid lesions to disease course in mucosal feline immunodeficiency virus type C infection.

    Science.gov (United States)

    Obert, L A; Hoover, E A

    2000-09-01

    Feline immunodeficiency virus (FIV) infection typically has a prolonged and variable disease course in cats, which can limit its usefulness as a model for human immunodeficiency virus infection. A clade C FIV isolate (FIV-C) has been associated with high viral burdens and rapidly progressive disease in cats. FIV-C was transmissible via oral-nasal, vaginal, or rectal mucosal exposure, and infection resulted in one of three disease courses: rapid, conventional/slow, or regressive. The severity of the pathologic changes paralleled the disease course. Thymic depletion was an early lesion and was correlated with detection of FIV RNA in thymocytes by in situ hybridization. The major changes in thymic cell populations were depletion of p55+/S100+ dendritic cells, CD3- cells, CD4+/CD8- cells, and CD4+/CD8+ cells and increases in apoptosis, CD45R+ B cells, and lymphoid follicles. In contrast to thymic depletion, peripheral lymphoid tissues often were hyperplastic. Mucosally transmitted FIV-C is thymotropic and induces a spectrum of lymphoid lesions and disease mirroring that seen with the human and simian immunodeficiency virus infections.

  7. Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

    Science.gov (United States)

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  8. NK cells and other innate lymphoid cells in haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Paola eVacca

    2016-05-01

    Full Text Available Natural Killer (NK cells play a major role in the T-cell depleted haploidentical haematopoietic stem cell transplantation (haplo-HSCT to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILC. At variance with NK cells, the other ILC populations (ILC1/2/3 are non-cytolytic, while they secrete different patterns of cytokines. ILC provide host defences against viruses, bacteria and parasites, drive lymphoid organogenesis, and contribute to tissue remodelling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defences that are reconstituted more rapidly than the adaptive ones. In this context, ILC may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodelling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILC. Of note, CD34+ cells isolated from different sources of HSC, may differentiate in vitro towards various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g. IL-1β may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  9. Characterization of the diffuse mucosal associated lymphoid tissue of feline small intestine.

    Science.gov (United States)

    Roccabianca, P; Woo, J C; Moore, P F

    2000-06-30

    Characterization of the feline intestinal mucosal associated lymphoid tissue (MALT) will facilitate investigation of intestinal disease in the cat and promote the cat as an animal model for a range of human diseases which involve the intestinal lymphoid tissue. This includes inflammatory bowel disease, viral and non-viral associated intestinal lymphomas and immunodeficiency associated syndromes. Morphologic and phenotypic characterization of the normal small intestinal diffuse MALT in 22 SPF cats was performed using flow cytometry and cytology on isolated intestinal leukocytes from the intra-epithelial and lamina proprial compartments, as well as immunohistology on tissues from the feline duodenum, jejunum and ileum. The intra-epithelial compartment (IEC) was dominated by lymphocytes (>85%) which frequently contained intracytoplasmic granules. The most striking findings in the IEC were the elevated percentages of CD8 alpha+ lymphocytes (40%), presumed to express CD8 alpha alpha chains, and CD4-/CD8- (double negative) lymphocytes (44%), and the consistent presence of a minor subpopulation of CD3+/CD11d+ IELs (6%). Small percentages of CD4+ lymphocytes (10%) were observed such that the IEL CD4:CD8 ratio (0.25) was low. The LPC also contained a majority of T cells and few plasma cells. However, this compartment had reduced percentages of CD8 alpha+ lymphocytes (28%) and increased percentages of CD4+ lymphocytes (27%) relative to the IEC. However, the LPL CD4:CD8 ratio (1.0) remained low compared with the ratio in peripheral blood. In feline MALT, MHC class II expression was lower than in other peripheral lymphoid compartments. The results of this study provide important reference values for future investigations involving feline intestinal lymphocytes and demonstrates that the leukocyte distribution and phenotypic characteristics of the feline diffuse MALT appear largely similar to the murine, rat and human counterparts.

  10. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  11. Ozone-Induced Type 2 Immunity in Nasal Airways. Development and Lymphoid Cell Dependence in Mice.

    Science.gov (United States)

    Ong, Chee Bing; Kumagai, Kazuyoshi; Brooks, Phillip T; Brandenberger, Christina; Lewandowski, Ryan P; Jackson-Humbles, Daven N; Nault, Rance; Zacharewski, Timothy R; Wagner, James G; Harkema, Jack R

    2016-03-01

    Inhalation exposures to ozone commonly encountered in photochemical smog cause airway injury and inflammation. Elevated ambient ozone concentrations have been epidemiologically associated with nasal airway activation of neutrophils and eosinophils. In the present study, we elucidated the temporal onset and lymphoid cell dependency of eosinophilic rhinitis and associated epithelial changes in mice repeatedly exposed to ozone. Lymphoid cell-sufficient C57BL/6 mice were exposed to 0 or 0.5 parts per million (ppm) ozone for 1, 2, 4, or 9 consecutive weekdays (4 h/d). Lymphoid cell-deficient, Rag2(-/-)Il2rg(-/-) mice were similarly exposed for 9 weekdays. Nasal tissues were taken at 2 or 24 hours after exposure for morphometric and gene expression analyses. C57BL/6 mice exposed to ozone for 1 day had acute neutrophilic rhinitis, with airway epithelial necrosis and overexpression of mucosal Ccl2 (MCP-1), Ccl11 (eotaxin), Cxcl1 (KC), Cxcl2 (MIP-2), Hmox1, Il1b, Il5, Il6, Il13, and Tnf mRNA. In contrast, 9-day ozone exposure elicited type 2 immune responses in C57BL/6 mice, with mucosal mRNA overexpression of Arg1, Ccl8 (MCP-2), Ccl11, Chil4 (Ym2), Clca1 (Gob5), Il5, Il10, and Il13; increased density of mucosal eosinophils; and nasal epithelial remodeling (e.g., hyperplasia/hypertrophy, mucous cell metaplasia, hyalinosis, and increased YM1/YM2 proteins). Rag2(-/-)Il2rg(-/-) mice exposed to ozone for 9 days, however, had no nasal pathology or overexpression of transcripts related to type 2 immunity. These results provide a plausible paradigm for the activation of eosinophilic inflammation and type 2 immunity found in the nasal airways of nonatopic individuals subjected to episodic exposures to high ambient ozone.

  12. Dendritic Cells Enhance HIV Infection of Memory CD4(+) T Cells in Human Lymphoid Tissues.

    Science.gov (United States)

    Reyes-Rodriguez, Angel L; Reuter, Morgan A; McDonald, David

    2016-02-01

    Dendritic cells (DCs) play a key role in controlling infections by coordinating innate and adaptive immune responses to invading pathogens. Paradoxically, DCs can increase HIV-1 dissemination in vitro by binding and transferring infectious virions to CD4(+) T cells, a process called transinfection. Transinfection has been well characterized in cultured cell lines and circulating primary T cells, but it is unknown whether DCs enhance infection of CD4(+) T cells in vivo. In untreated HIV infection, massive CD4(+) T-cell infection and depletion occur in secondary lymphoid tissues long before decline is evident in the peripheral circulation. To study the role of DCs in HIV infection of lymphoid tissues, we utilized human tonsil tissues, cultured either as tissue blocks or as aggregate suspension cultures, in single-round infection experiments. In these experiments, addition of monocyte-derived DCs (MDDCs) to the cultures increased T-cell infection, particularly in CD4(+) T cells expressing lower levels of HLA-DR. Subset analysis demonstrated that MDDCs increased HIV-1 infection of central and effector memory T-cell populations. Depletion of endogenous myeloid DCs (myDCs) from the cultures decreased memory T-cell infection, and readdition of MDDCs restored infection to predepletion levels. Using an HIV-1 fusion assay, we found that MDDCs equally increased HIV delivery into naïve, central, and effector memory T cells in the cultures, whereas predepletion of myDCs reduced fusion into memory T cells. Together, these data suggest that resident myDCs facilitate memory T-cell infection in lymphoid tissues, implicating DC-mediated transinfection in driving HIV dissemination within these tissues in untreated HIV/AIDS.

  13. Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2016-06-01

    Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

  14. A clinically attainable dose of L-asparaginase targets glutamine addiction in lymphoid cell lines.

    Science.gov (United States)

    Sugimoto, Koichi; Suzuki, Hiroshi I; Fujimura, Tsutomu; Ono, Asami; Kaga, Naoko; Isobe, Yasushi; Sasaki, Makoto; Taka, Hikari; Miyazono, Kohei; Komatsu, Norio

    2015-11-01

    L-asparaginase (L-ASNase) is an important branch of chemotherapy for acute lymphoblastic leukemia (ALL) and some types of non-Hodgkin's lymphoma, including natural killer (NK)-cell lymphoma. Although it mediates hydrolysis of asparagine (Asn) and glutamine (Gln), which are variably required for cancer cell survival, the relative contribution of Asn and Gln depletion to the anti-tumor activity in therapeutic doses is unclear in ALL and malignant lymphoma. Here we demonstrate that L-ASNase exerts cytotoxicity through targeting the Gln addiction phenotype in lymphoid cell lines. A clinically attainable intermediate dose of L-ASNase induced massive apoptosis in ALL Jurkat and mantle cell lymphoma Jeko cell lines, while a low dose of L-ASNase effectively killed NK-cell lymphoma cells. In the lymphoid cell lines Jurkat and Jeco, deprivation of Gln but not Asn specifically suppressed cell growth and survival, and phenocopied the action of L-ASNase. L-ASNase treatment and Gln deprivation dramatically disrupted the refilling of the tricarboxylic acid (TCA) cycle by intracellular glutamate (Glu) and disturbed the mitochondrial integrity, which were alleviated by various anaplerotic TCA cycle intermediates, suggesting a direct contribution of glutaminase activity of L-ASNase. The action of L-ASNase differs between Jurkat cells and NK-cell lymphoma cells, according to their dependence on Gln and Asn. Furthermore, we observed that high expression of glutaminase GLS1 is associated with increased sensivity to L-ASNase in pediatric B lineage ALL. Our results redefine L-ASNase as a therapeutic agent targeting Gln addiction in certain lymphoid cells and offer an additional basis for predicting L-ASNase sensitivity and engineering selective L-ASNase derivatives for leukemia and lymphoma.

  15. Theileria parva: effects of irradiation on a culture of parasitized bovine lymphoid cells. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Irvin, A.D.; Brown, C.G.D.; Stagg, D.A.

    1975-01-01

    Aliquots of a culture of Theileria parva-infected bovine lymphoid cells were irradiated at 0, 300, 600, 900, and 1200 rads. The short-term effects of irradiation were evaluated on examination of Giemsa-stained smears and on autoradiography of cells labeled with (/sup 3/H)thymidine. Irradiation inhibited cell division but parasite division did not appear to be inhibited and macroschizont nuclear particles increased in number, frequently to several hundred per schizont. There was no evidence of an increased percentage switch from macro- to microschizont. Apparently viable cells were still present in all cultures 4 days after irradiation.

  16. Endoscopic features of lymphoid follicles in Helicobacter pylori-associated chronic gastritis.

    Science.gov (United States)

    Hayashi, Seishu; Imamura, Jun; Kimura, Kiminori; Saeki, Shunichi; Hishima, Tsunekazu

    2015-01-01

    Small, round, yellowish-white nodules (YWN) are frequently observed in Helicobacter pylori-associated gastritis. The aim of the present study was to investigate the clinical significance of these YWN. Participants comprised 211 patients with H. pylori-associated gastritis, ranging in age from 23 to 86 years. YWN were detected in 23% of participants, more frequently in women (33%) than in men (12%; P gastritis, and represented histological lymphoid follicles. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

  17. Primary mucosa-associated lymphoid tissue thyroid lymphoma: a rare thyroid neoplasm of extrathyroid origin

    Directory of Open Access Journals (Sweden)

    Dimitrios Hadjidakis

    2012-01-01

    Full Text Available Primary thyroid lymphoma is a rare malignancy, representing 2-8% of all thyroid malignancies and 1-2% of all extranodal lymphomas. The majority of cases concern non-Hodgkin`s lymphoma of B cell origin, following by Hodgkin’s disease, T cell lymphomas and rarely marginal zone B-cell mucosa-associated lymphoid tissue (MALT lymphomas. MALT lymphomas have been associated with long-standing autoimmune Hashimoto`s thyroiditis. We present the case of a 44-years-old woman with thyroid MALT lymphoma in the background of multinodular goiter of autoimmune origin.

  18. Employment of whole-body. gamma. -irradiation in chronic lymphoid leukemia and malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Danilova, N.B.; Baranov, A.E.; Khrushchev, V.G.; Grammatikati, V.S.; Murav' eva, L.I.; Strashnenko, E.S.

    1982-11-01

    There are presented data showing that whole-body therapeutic ..gamma..-irradiation is an effective method of treatment of chronic lymphoid leukosis and lymphomas. Rapid lymphopenic effect, satisfactory diminution of lymph nodes and spleen sizes testify to the effect. The necessity of further investigation of the treatment method is underlined. It is of interest to trace the fate of lymphocyte subpopulations in the course and after treatment. The urgency of working out a most rational scheme for whole-body therapeutic irradiation and for investigating indications for local irradiation of various groups of lymphatic nodes is indicated.

  19. Heart and kidney transplantation using total lymphoid irradiation and donor bone marrow in mongrel dogs

    Energy Technology Data Exchange (ETDEWEB)

    Kahn, D.R.; Dufek, J.H.; Hong, R.; Caldwell, W.L.; Thomas, F.J.; Kolenda, D.R.; Swanson, D.K.; Struble, R.A.

    1980-07-01

    Heart and kidney allografts showed markedly prolonged survival in unrelated mongrel dogs following total lymphoid irradiation (TLI) and donor bone marrow without any other immunosuppression. In every animal the heart survived longer than the kidney. Placing the kidney allograft in the abdomen with the bone marrow given intraperitoneally doubled kidney survival over placement in the neck, but heart survival was equally prolonged in the abdomen or neck. Splenectomy before TLI or after TLI, but just before transplantation, almost completely eliminated the prolonged survival of both heart and kidney allografts. Thus there is suggestive evidence that TLI plus bone marrow from the donor may be valuable for transplantation in man, particularly heart transplantation.

  20. Treatment of acute non-lymphoid leukemias: comparison of two protocols.

    Science.gov (United States)

    Hauptmann, E; Stacher, A; Heinz, R; Jaksic, B

    1977-12-19

    The results of treatment of 57 patients suffering from acute non-lymphoid leukemia by two protocols are compared. The more aggressive Coap protocol rendered a higher remission rate (57.1%), than the mild Guyer protocol where the remission rate has been 25%. The best results have been achieved in the former group in the younger population; in the latter group there has been no age-effect relationship. Although the remission rate differed in both protocols there has been no statistically significant difference in survival.

  1. Innate lymphoid cells and cytokines of the novel subtypes of helper T cells in asthma

    OpenAIRE

    Sherkat, Roya; Yazdani, Reza; Ganjalikhani Hakemi, Mazdak; Homayouni, Vida; Farahani, Rahim; Hosseini, Mohsen; Rezaei, Abbas

    2014-01-01

    Background In this study, the expression of interleukin-9 (IL-9), IL-17, IL-22, and IL-25 genes that might be the potential predisposing factors for asthma as well as count of innate lymphoid cells (ILCs) as another source of inflammatory cytokines have been evaluated. Objective The aim of this study was to evaluate the expression of newly identified helper T cells signature cytokines and amount of ILCs. Methods Blood and sputum samples from 23 patients with moderate to severe asthma and 23 h...

  2. Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

    Energy Technology Data Exchange (ETDEWEB)

    Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

    1987-11-01

    We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases.

  3. Organizing the thymus gland.

    Science.gov (United States)

    Muñoz, Juan José; García-Ceca, Javier; Alfaro, David; Stimamiglio, Marco Augusto; Cejalvo, Teresa; Jiménez, Eva; Zapata, Agustín G

    2009-02-01

    Eph receptors and their ligands, ephrins, are molecules involved in the morphogenesis of numerous tissues, including the central nervous system in which they play a key role in determining cell positioning and tissue domains containing or excluding nerve fibers. Because common features have been suggested to occur in the microenvironmental organization of brain and thymus, a highly compartmentalized organ central for T cell differentiation, we examined the expression and possible role of Eph/ephrins in the biology of the thymus gland. We reviewed numerous in vivo and in vitro results that confirm a role for Eph and ephrins in the maturation of the thymic epithelial cell (TEC) network and T cell differentiation. Their possible involvement in different steps of early thymus organogenesis, including thymus primordium branching, lymphoid colonization, and thymocyte-TEC interactions, that determine the organization of a mature three-dimensional thymic epithelial network is also analyzed.

  4. E2F4 modulates differentiation and gene expression in hematopoietic progenitor cells during commitment to the lymphoid lineage.

    Science.gov (United States)

    Enos, Megan E; Bancos, Simona A; Bushnell, Timothy; Crispe, Ian N

    2008-03-15

    The E2F4 protein is involved in gene repression and cell cycle exit, and also has poorly understood effects in differentiation. We analyzed the impact of E2F4 deficiency on early steps in mouse hematopoietic development, and found defects in early hematopoietic progenitor cells that were propagated through common lymphoid precursors to the B and T lineages. In contrast, the defects in erythromyeloid precursor cells were self-correcting over time. This suggests that E2F4 is important in early stages of commitment to the lymphoid lineage. The E2F4-deficient progenitor cells showed reduced expression of several key lymphoid-lineage genes, and overexpression of two erythromyeloid lineage genes. However, we did not detect effects on cell proliferation. These findings emphasize the significance of E2F4 in controlling gene expression and cell fate.

  5. Role of Sphingosine 1-Phosphate Receptor Type 1 in Lymphocyte Egress from Secondary Lymphoid Tissues and Thymus

    Institute of Scientific and Technical Information of China (English)

    Kenji Chiba; Hirofumi Matsuyuki; Yasuhiro Maeda; Kunio Sugahara

    2006-01-01

    Circulation of mature lymphocytes between blood and secondary lymphoid tissues plays a central role in the immune system. Homing of lymphocytes from blood into secondary lymphoid tissues beyond high endothelial venules is highly dependent on the interaction between the chemokines CCL19, CCL21, CXCL12, and CXCL13,and their receptors CCR7, CXCR4 and CXCR5. However, the molecular mechanism(s) of lymphocyte egress from secondary lymphoid tissues to lymph remained unclear. We have found a new class of immunomodulator, FTY720 by chemical modification of vegetative wasp-derived natural product, ISP-I (myriocin). FTY720 has been shown to be highly effective in experimental allograft and autoimmune disease models. A striking feature of FTY720 is the induction of a marked decrease in peripheral blood lymphocytes at doses that show immunomodulating activity in these models. The reduction of circulating lymphocytes by FTY720 is caused by sequestration of iymphocytes into secondary lymphoid tissues and thymus. FTY720 is rapidly converted to (S)-enantiomer of FTY720-phosphate[(S)-FTY720-P] by sphingosine kinase 2 in vivo. (S)-FTY720-P acting as a potent agonist of S1P receptor type 1(S1P1), induces long-term down-regulation of S1P1 on lymphocytes, and thereby inhibits the migration of lymphocytes toward S1P. Thus, it is presumed that FTY720-induced lymphocyte sequestration is due to the inhibition of S1P/S1P1-dependent lymphocyte egress from secondary lymphoid tissues and thymus by its active metabolite (S)-FTY720-P. Throughout the analysis of the mechanism of action of FTY720, it is clarified that S1P/S1P1 interaction plays an important role for lymphocyte egress from secondary lymphoid tissues and thymus.

  6. Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.

    Directory of Open Access Journals (Sweden)

    Francois P Duhoux

    Full Text Available Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27 and telomeric rearrangements (N = 15, both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39, mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18(q32;q21 as well as follicular lymphomas without t(14;18]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

  7. Gata3 drives development of RORγt+ group 3 innate lymphoid cells

    Science.gov (United States)

    Serafini, Nicolas; Klein Wolterink, Roel G.J.; Satoh-Takayama, Naoko; Xu, Wei; Vosshenrich, Christian A.J.; Hendriks, Rudi W.

    2014-01-01

    Group 3 innate lymphoid cells (ILC3) include IL-22–producing NKp46+ cells and IL-17A/IL-22–producing CD4+ lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal RORγt+ ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut RORγt+ ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets. PMID:24419270

  8. Bronchus-associated lymphoid tissue (BALT and survival in a vaccine mouse model of tularemia.

    Directory of Open Access Journals (Sweden)

    Damiana Chiavolini

    Full Text Available BACKGROUND: Francisella tularensis causes severe pulmonary disease, and nasal vaccination could be the ideal measure to effectively prevent it. Nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant. METHODOLOGY/PRINCIPAL FINDINGS: Mice were immunized via the nasal route with lipopolysaccharide isolated from F. tularensis and neisserial recombinant PorB as an adjuvant candidate. Then, mice were challenged via the same route with the F. tularensis attenuated live vaccine strain (LVS. Mouse survival and analysis of a number of immune parameters were conducted following intranasal challenge. Vaccination induced a systemic antibody response and 70% of mice were protected from challenge as showed by their improved survival and weight regain. Lungs from mice recovering from infection presented prominent lymphoid aggregates in peribronchial and perivascular areas, consistent with the location of bronchus-associated lymphoid tissue (BALT. BALT areas contained proliferating B and T cells, germinal centers, T cell infiltrates, dendritic cells (DCs. We also observed local production of antibody generating cells and homeostatic chemokines in BALT areas. CONCLUSIONS: These data indicate that PorB might be an optimal adjuvant candidate for improving the protective effect of F. tularensis antigens. The presence of BALT induced after intranasal challenge in vaccinated mice might play a role in regulation of local immunity and long-term protection, but more work is needed to elucidate mechanisms that lead to its formation.

  9. Epstein-Barr virus (EBV)-associated lymphoid lesions of the head and neck.

    Science.gov (United States)

    Auerbach, Aaron; Aguilera, Nadine S

    2015-01-01

    Epstein Barr virus (EBV)-related lymphoproliferative processes occur in the head and neck ranging from reactive processes such as infectious mononucleosis to high grade malignant lymphomas. EBV is a ubiquitous herpes virus that infects more than 90% of adults worldwide, and is generally transferred though saliva. Primary infection can occur throughout life. EBV is the first virus linked to malignancies, both epithelial and lymphoid. Both T and B cell lymphomas can be associated with EBV and evidence shows that an individual's response to the acute EBV infection may be critical in the development of subsequent lymphoma. Currently, in situ hybridization for EBER is the most sensitive available test to detect EBV and should be routinely performed in lymphoproliferative lesions of the head and neck. Immunohistochemistry for EBV related proteins, such as LMP1, is much less sensitive than EBER in situ hybridization, but can help determine latency patterns of EBV infection. Although relatively rare, primary EBV-related lymphomas must be considered in the differential of atypical lymphoid proliferations in the head and neck. We present selected EBV-related disorders of the head and neck discussing etiology as well as differential diagnosis.

  10. Clinical characteristics of a group of adults with nodular lymphoid hyperplasia: A single center experience

    Institute of Scientific and Technical Information of China (English)

    Alberto Rubio-Tapia; Jorge Hernéndez-Calleros; Sagrario Trinidad-Hernández; Luis Uscanga

    2006-01-01

    AIM: To describe the clinical and histological characteristics of a group of adults with small-bowel nodular lymphoid hyperplasia (NLH).METHODS: Patients were searched for five years in pathology records of our institution. The biopsy material was reassessed using strict histopathological criteria.Clinical data were obtained from medical records.RESULTS: Small-bowel NLH was diagnosed in 18 cases.The female: male ratio was 2: 1. The most frequent symptoms were diarrhea (72%), involuntary weight loss (72%) and abdominal pain (61%). Nine patients (50%)had immunodeficiency. Small-bowel bacterial overgrowth was found in three (17%) cases. At small-bowel NLH diagnosis, three (17%) had associated lymphoma: two intestinal and one extra-intestinal lymphomas. In two patients with villous atrophy and anti-endomysial antibodies the diagnosis of celiac disease was established.Giardia lamblia infection was found in only one patientwith hypogammaglobulinemia (Herman's syndrome).CONCLUSIONS; NLH is uncommon in adult patients.Associated diseases are immunodeficiency and lymphoid tissue malignancies.

  11. A novel IL-10-producing innate lymphoid cells (ILC10) in a contact hypersensitivity mouse model

    Science.gov (United States)

    Kim, Hyuk Soon; Jang, Jong-Hwa; Lee, Min Bum; Jung, In Duk; Park, Yeong-Min; Kim, Young Mi; Choi, Wahn Soo

    2016-01-01

    The immunoregulatory cytokine Interleukin 10 (IL-10) protein is produced by various cells during the course of inflammatory disorders. Mainly, it downregulates pro-inflammatory cytokines, antigen presentation, and helper T cell activation. In this study, we show that the ratio of IL-10-producing cells was significantly increased in lineage negative (i.e., not T, B, or leukocyte cell lineages) cells than in lineage positive cells in lymphoid and peripheral tissues. We further observed that IL-10-producing innate lymphoid cells (ILCs), here called firstly ILC10, were increased in number in oxazolone-induced contact hypersensitivity (CHS) mice. In detail, IL-10-producing lineage negative cells were elevated in the axillary, inguinal lymph node, and ear tissues of CHS mice. Notably, the cells expressed classical ILC marker proteins such as CD45, CD127, and Sca-1. Altogether, our findings suggest for the first time that ILC10s are present in various physiological settings and could be involved in numerous immune responses as regulatory cells. [BMB Reports 2016; 49(5): 293-296] PMID:26949018

  12. IL-23 activates innate lymphoid cells to promote neonatal intestinal pathology.

    Science.gov (United States)

    Chen, L; He, Z; Slinger, E; Bongers, G; Lapenda, T Ls; Pacer, M E; Jiao, J; Beltrao, M F; Soto, A J; Harpaz, N; Gordon, R E; Ochando, J C; Oukka, M; Iuga, A C; Chensue, S W; Blander, J M; Furtado, G C; Lira, S A

    2015-03-01

    Interleukin-23 (IL-23) responsive group 3 innate lymphoid cells (ILC3s) have been implicated in immune homeostasis and pathogenesis in the adult, but little is known about their roles in the newborn. Here we show that IL-23 promotes conversion of embryonic intestinal Lin(-)IL-23R(+)Thy1(+) cells into IL-22-producing Thy1(+)Sca-1(hi) ILC3s in vitro. Gut-specific expression of IL-23 also activated and expanded Thy1(+)Sca-1(hi) ILC3s, which produced IL-22, IL-17, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) and were distinct from canonical CD4(+) lymphoid tissue inducer (LTi) cells. These ILC3s accumulated under the epithelium in intercellular adhesion molecule (ICAM)-1-positive cell aggregates together with neutrophils that disrupted the epithelium, leading to the formation of discrete intestinal erosions, bleeding, and neonatal death. Genetic and antibody depletion of ILC3s rescued the mice from neonatal death. Antibiotic treatment of pregnant mothers and offspring prolonged survival of IL-23 transgenic mice, suggesting a role for the commensal flora on ILC3-induced pathogenesis. Our results reveal a novel role for the IL-23-ILC3s axis in the pathogenesis of neonatal intestinal inflammation.

  13. TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

    Directory of Open Access Journals (Sweden)

    Elisa Dorantes-Acosta

    2013-01-01

    Full Text Available Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.

  14. An Overview of the Role of Innate Lymphoid Cells in Gut Infections and Inflammation

    Directory of Open Access Journals (Sweden)

    Silvia Sedda

    2014-01-01

    Full Text Available Innate lymphoid cells (ILCs are a group of hematopoietic cells devoid of antigen receptors that have important functions in lymphoid organogenesis, in the defense against extracellular pathogens, and in the maintenance of the epithelial barrier. Three distinct groups of ILCs have been identified on the basis of phenotypic and functional criteria and termed ILCs1, ILCs2, and ILCs3. Specifically, ILCs1 express the transcription factor T-bet and secrete T helper type-1- (Th1- related cytokines, ILCs2 are dependent on the transcription factor RORα and express Gata-3 and the chemokine receptor homologous molecule (CRTH2 and produce Th2-related cytokines, and ILCs3 express the transcription factor RORγt and synthesize interleukin- (IL- 17, IL-22, and, under specific stimuli, interferon-γ. ILCs represent a relatively small population in the gut, but accumulating evidence suggests that these cells could play a decisive role in orchestrating both protective and detrimental immune responses. In this review, we will summarize the present knowledge on the distribution of ILCs in the intestinal mucosa, with particular focus on their role in the control of both infections and effector cytokine response in immune-mediated pathologies.

  15. A human postnatal lymphoid progenitor capable of circulating and seeding the thymus.

    Science.gov (United States)

    Six, Emmanuelle M; Bonhomme, Delphine; Monteiro, Marta; Beldjord, Kheira; Jurkowska, Monika; Cordier-Garcia, Corinne; Garrigue, Alexandrine; Dal Cortivo, Liliane; Rocha, Benedita; Fischer, Alain; Cavazzana-Calvo, Marina; André-Schmutz, Isabelle

    2007-12-24

    Identification of a thymus-seeding progenitor originating from human bone marrow (BM) constitutes a key milestone in understanding the mechanisms of T cell development and provides new potential for correcting T cell deficiencies. We report the characterization of a novel lymphoid-restricted subset, which is part of the lineage-negative CD34(+)CD10(+) progenitor population and which is distinct from B cell-committed precursors (in view of the absence of CD24 expression). We demonstrate that these Lin(-)CD34(+)CD10(+)CD24(-) progenitors have a very low myeloid potential but can generate B, T, and natural killer lymphocytes and coexpress recombination activating gene 1, terminal deoxynucleotide transferase, PAX5, interleukin 7 receptor alpha, and CD3epsilon. These progenitors are present in the cord blood and in the BM but can also be found in the blood throughout life. Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus.

  16. Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging.

    Science.gov (United States)

    Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina; Morita, Yohei; Rudolph, Karl Lenhard

    2016-04-01

    Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways.

  17. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

    Science.gov (United States)

    Cautivo, Kelly M; Molofsky, Ari B

    2016-06-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or "allergic" immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT "browning," and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis.

  18. Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues.

    Science.gov (United States)

    Tabibian-Keissar, Hilla; Hazanov, Lena; Schiby, Ginette; Rosenthal, Noemie; Rakovsky, Aviya; Michaeli, Miri; Shahaf, Gitit Lavy; Pickman, Yishai; Rosenblatt, Kinneret; Melamed, Doron; Dunn-Walters, Deborah; Mehr, Ramit; Barshack, Iris

    2016-02-01

    The elderly immune system is characterized by reduced responses to infections and vaccines, and an increase in the incidence of autoimmune diseases and cancer. Age-related deficits in the immune system may be caused by peripheral homeostatic pressures that limit bone marrow B-cell production or migration to the peripheral lymphoid tissues. Studies of peripheral blood B-cell receptor spectratypes have shown that those of the elderly are characterized by reduced diversity, which is correlated with poor health status. In the present study, we performed for the first time high-throughput sequencing of immunoglobulin genes from archived biopsy samples of primary and secondary lymphoid tissues in old (74 ± 7 years old, range 61-89) versus young (24 ± 5 years old, range 18-45) individuals, analyzed repertoire diversities and compared these to results in peripheral blood. We found reduced repertoire diversity in peripheral blood and lymph node repertoires from old people, while in the old spleen samples the diversity was larger than in the young. There were no differences in somatic hypermutation characteristics between age groups. These results support the hypothesis that age-related immune frailty stems from altered B-cell homeostasis leading to narrower memory B-cell repertoires, rather than changes in somatic hypermutation mechanisms.

  19. Clonal rearrangements of immunoglobulin genes and progression to B cell lymphoma in cutaneous lymphoid hyperplasia.

    Science.gov (United States)

    Wood, G S; Ngan, B Y; Tung, R; Hoffman, T E; Abel, E A; Hoppe, R T; Warnke, R A; Cleary, M L; Sklar, J

    1989-07-01

    Cutaneous lymphoid hyperplasia (CLH) is a disorder characterized by the development of one or more skin lesions containing dense lymphoid infiltrates that exhibit the histopathologic features of a benign, reactive process. Nevertheless, some cases have been associated with the subsequent development of clinically overt lymphomas. This suggests that monoclonal populations may exist in some cases of CLH and that these cases may represent a subset more likely to evolve into lymphoma. To determine if such a subset of CLH can be distinguished, Southern blot analysis of DNA was used to study the immunogenotypic features of lesions from 14 patients with clinical, histopathologic, and immunopathologic findings characteristic of CLH. Five cases exhibited detectable clonal rearrangements of immunoglobulin genes. Furthermore, one of these five cases evolved into overt diffuse large cell lymphoma of B cell lineage during a 2-year follow-up of recurrent disease at the original cutaneous site. The immunoglobulin gene rearrangements of this lymphoma were identical to those of the prior CLH lesion. There was no evidence of detectable t(14;18) chromosomal translocations or clonal rearrangements of the beta gene of the T cell receptor in any case. It was concluded that CLH can be divided into two subsets based on the presence or absence of a clonal B cell population, and that overt lymphoma can arise from the former subset and contain the same B cell clone identified in the pre-existent CLH lesion.

  20. Reactive lymphoid hyperplasia of the liver: A case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A case of a 53-year-old female patient with reactive lymphoid hyperplasia (RLH), clinically designated as pseudolymphoma of the liver is described in this article. The patient was admitted to our hospital for further evaluation of hepatic tumors incidentally discovered at another hospital. Various diagnostic methods, including ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI) and hepatic angiography displayed three small lesions in the liver with outstanding findings consistent with hepatocellular carcinoma (HCC). Surgical resection was performed and the three lesions were microscopically diagnosed as RLH of the liver. The lesions comprised a massive infiltration of lymphoid cells with follicles and hyalinized interfollicular spaces. Immunohistochemical examination revealed that infiltrating lymphocytes had no prominent nuclear atypia and polyclonality. RLH of the liver is a very rare condition and only twelve cases have been reported in the English literature. Majority of the reported cases were middle-aged women and about half of them had some immunologic abnormalities such as autoimmune thyroiditis, Sjogren's syndrome, primary immunodeficiency, primary biliary cirrhosis. Since they are often clinically misdiagnosed as HCC, surgery is the choice of treatment for these patients. Although their pathology resembles malignant lymphoma, the clinical course is completely benign. The authors propose that RLH of the liver can be discriminated from HCC by its clinical features.

  1. Cytokine Receptor Expression in Human Lymphoid Tissue: Analysis by Fluorescence Microscopy

    Directory of Open Access Journals (Sweden)

    Heddy Zola

    1994-01-01

    Full Text Available A highl y-sen sitile tlourescence method, capable of detecting cytokine receptors present at low concentrations (around I DO molecules per cell by flow cytometry, was adapted for use on tissue sections. This method was used to examine the expression of several cytokine receptors in lymphoid ti ss ues. lL-2 receptors were distributed broadly, with higher concentrations in T cell areas. lL-1 receptor Type I was detected in T cell areas and in the follicular mantle, and was strongly expressed on vasc ular endothelium. IL-6 receptor was found at very low concentration, both within and outside germinal centres. The gp 130 molecule, which is involved in the functional receptor complex for IL-6 and several other cytokines, was present at higher concentrations, particularly in the germinal centre. Analysis of receptor expression in secondary lymphoid tissue provides evidence bearing on the physiological roles of cytokines, as these tissues contain cells at various stages of physiological activation located in well-defined functional zones.

  2. Characterization and Quantification of Innate Lymphoid Cell Subsets in Human Lung.

    Directory of Open Access Journals (Sweden)

    Katrien C De Grove

    Full Text Available Innate lymphoid cells (ILC are a new family of innate immune cells that have emerged as important regulators of tissue homeostasis and inflammation. However, limited data are available concerning the relative abundance and characteristics of ILC in the human lung.The aim of this study was to characterize and enumerate the different ILC subsets in human lung by multi-color flow cytometry.Within the CD45+ Lin- CD127+ pulmonary ILC population, we identified group 1 (ILC1, group 2 (ILC2 and group 3 (ILC3 innate lymphoid cells using specific surface markers (i.e. IL12Rβ2, CRTH2 and CD117 respectively and key transcription factors (i.e. T-bet, GATA-3 and RORγT respectively. Based on the presence of NKp44, ILC3 were further subdivided in natural cytotoxicity receptor (NCR+ and NCR- ILC3. In addition, we demonstrated the production of signature cytokines IFN-γ, IL-5, IL-17A, IL-22 and GM-CSF in the pulmonary ILC population. Interestingly, we observed a tendency to a higher frequency of NCR- ILC3 in lungs of patients with chronic obstructive pulmonary disease (COPD compared with controls.We show that the three main ILC subsets are present in human lung. Importantly, the relative abundance of ILC subsets tended to change in COPD patients in comparison to control individuals.

  3. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation

    Science.gov (United States)

    Romero-Camarero, Isabel; Jiang, Xiaoyu; Natkunam, Yasodha; Lu, Xiaoqing; Vicente-Dueñas, Carolina; Gonzalez-Herrero, Ines; Flores, Teresa; Garcia, Juan Luis; McNamara, George; Kunder, Christian; Zhao, Shuchun; Segura, Victor; Fontan, Lorena; Martínez-Climent, Jose A.; García-Criado, Francisco Javier; Theis, Jason D.; Dogan, Ahmet; Campos-Sánchez, Elena; Green, Michael R.; Alizadeh, Ash A.; Cobaleda, Cesar; Sánchez-García, Isidro; Lossos, Izidore S.

    2012-01-01

    The human germinal centre associated lymphoma (HGAL) gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that HGAL directly binds Syk in B-cells, increases its kinase activity upon B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, HGAL transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive AA amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the HGAL transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein HGAL regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation. PMID:23299888

  4. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.

    Science.gov (United States)

    Romero-Camarero, Isabel; Jiang, Xiaoyu; Natkunam, Yasodha; Lu, Xiaoqing; Vicente-Dueñas, Carolina; Gonzalez-Herrero, Ines; Flores, Teresa; Garcia, Juan Luis; McNamara, George; Kunder, Christian; Zhao, Shuchun; Segura, Victor; Fontan, Lorena; Martínez-Climent, Jose A; García-Criado, Francisco Javier; Theis, Jason D; Dogan, Ahmet; Campos-Sánchez, Elena; Green, Michael R; Alizadeh, Ash A; Cobaleda, Cesar; Sánchez-García, Isidro; Lossos, Izidore S

    2013-01-01

    The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.

  5. Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells

    Science.gov (United States)

    Scoville, Steven D.; Freud, Aharon G.; Caligiuri, Michael A.

    2017-01-01

    Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development. PMID:28396671

  6. Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas.

    Science.gov (United States)

    Ménard, S; Tomasic, G; Casalini, P; Balsari, A; Pilotti, S; Cascinelli, N; Salvadori, B; Colnaghi, M I; Rilke, F

    1997-05-01

    Infiltration by lymphoid cells is a common feature of many human tumors, including breast carcinomas, and the degree of infiltration has been suggested to be a measure of the host immune response. Our analyses in a series of 1919 cases of primary ductal and lobular infiltrating breast carcinomas from women with a long-term follow-up revealed: (a) a 16-17% frequency of infiltrated tumors independent of the patient's age at diagnosis; and (b) a strong positive correlation between survival rates and the presence of lymphocytes at the tumor site in patients less than 40 years of age (P = 0.0002) but no association with prognosis in patients 40 years of age or older. Multivariate analysis indicated that lymphoid infiltration is independent of other conventional prognostic factors such as nodal status and tumor size in predicting survival. Thus, a possible immune response against the tumor seems to be relevant only in women with early-onset tumors. Because the immune system is functionally maximum in younger years, declining with age, this finding might reflect a difference in the efficiency of the immune system. Alternatively, the biology of these tumors might differ, leading to a difference in immuno-genicity.

  7. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-Infection in the Absence of Viral Suppression

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N.; Kazer, Samuel W.; Mjösberg, Jenny

    2016-01-01

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-on ILCs remains unknown. We found that human blood...... ILCs were severely depleted during acute viremic HIV-infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed...... mechanistic link between acute HIV-infection, lymphoid tissue breakdown, and persistent immune dysfunction....

  8. Long non-coding RNA profiling of human lymphoid progenitor cells reveals transcriptional divergence of B cell and T cell lineages.

    Science.gov (United States)

    Casero, David; Sandoval, Salemiz; Seet, Christopher S; Scholes, Jessica; Zhu, Yuhua; Ha, Vi Luan; Luong, Annie; Parekh, Chintan; Crooks, Gay M

    2015-12-01

    To elucidate the transcriptional 'landscape' that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitor cells spanning the earliest stages of B lymphoid and T lymphoid specification. Over 3,000 genes encoding previously unknown long non-coding RNAs (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage specific and were more lineage specific than those of protein-coding genes. Protein-coding genes co-expressed with neighboring lncRNA genes showed enrichment for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships among the earliest progenitor cells in the human bone marrow and thymus.

  9. Immunohistochemical characterization of selected cell markers for the detection of hematopoietic cells in formalin-fixed, paraffin wax-embedded lymphoid tissues of harbor seals (Phoca vitulina) and walruses (Odobenus rosmarus rosmarus).

    Science.gov (United States)

    Seibel, H; Stimmer, L; Siebert, U; Beineke, A

    2010-10-15

    To facilitate a detailed investigation of pinniped lymphoid organs, 30 monoclonal antibodies (mAb) as well as eight polyclonal antibodies (pAb) of different species specificities directed against cell antigens of the hematopoietic system were tested for immunohistochemical cross-reactivity on formalin-fixed, paraffin wax-embedded tissues of harbor seals (Phoca vitulina) and a walrus (Odobenus rosmarus rosmarus). Six monoclonal and eight polyclonal antibodies showed specific immunoreactivities. Lymphocytes were immunolabeled by an anti-CD3 pAb, anti-Foxp3 mAb and anti-CD79 alpha mAb, while plasma cell subpopulations were recognized by anti-IgA pAb, anti-IgG pAb and anti-IgM pAb as well as by anti-kappa- and anti-lambda light chain pAb. Cells of the histiocytic lineage were recognized by lysozyme-, myeloid/histiocyte antigen-, and CD68-specific markers. Furthermore, dendritic cell-like cells were detected by an anti-S100 protein pAb. The MHC class II antigen was labeled on the majority of immune cells of the harbor seal and walrus using a bovine mAb. Mast cells were stained by an anti-mast cell tryptase mAb. Thus, using these antibodies from various species, it is now possible to determine phenotypical changes in lymphoid organs and detect different leukocyte subsets involved in inflammatory responses in archived tissue samples of these pinniped species.

  10. Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis. [X radiation, mice

    Energy Technology Data Exchange (ETDEWEB)

    Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

    1978-12-01

    The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log/sub 10/PD/sub 50/ values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplanted Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain.

  11. Increased prevalence of lymphoid tissue inducer cells in the cerebrospinal fluid of patients with early multiple sclerosis

    DEFF Research Database (Denmark)

    Degn, Matilda; Modvig, Signe; Dyring-Andersen, Beatrice;

    2016-01-01

    BACKGROUND: Inflammatory cytokines produced by cells of the immune system are believed to play a central role in the pathogenesis of multiple sclerosis (MS). Innate lymphoid cells (ILCs) have been shown to produce and secrete a wide range of the cytokines involved in MS pathogenesis; however...... new knowledge beneficial for future MS therapies....

  12. The clinical characteristics and prognostic analysis of gastric mucosa-associated lymphoid tissue lymphoma of 103 cases

    Institute of Scientific and Technical Information of China (English)

    李晓武

    2012-01-01

    Objective To analyze the clinical characteristics and prognosis of the patients with gastric mucosa-associated lymphoid tissue(MALT) lymphoma. Methods The clinical characteristics and prognostic factors of 103 gastric MALT lymphoma patients admitted to our hospital from April 2001 to August 2011 were

  13. Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma

    NARCIS (Netherlands)

    R.G.J. Klein Wolterink (Roel); A. Kleinjan (Alex); M. van Nimwegen (Menno); I.M. Bergen (Ingrid); M.J.W. de Bruijn (Marjolein); Y. Levani (Yelvi); R.W. Hendriks (Rudi)

    2012-01-01

    textabstractAllergic asthma is characterized by chronic airway inflammation and hyperreactivity and is thought to be mediated by an adaptive T helper-2 (Th2) cell-type immune resp-onse. Here, we demonstrate that type 2 pulmonary innate lymphoid cells (ILC2s) significantly contribute to production of

  14. Incidence of Myelofibrosis in Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphoid Leukemia during Various Phases of Diseases.

    Science.gov (United States)

    Dolgikh, T Yu; Domnikova, N P; Tornuev, Yu V; Vinogradova, E V; Krinitsyna, Yu M

    2017-02-01

    Pathomorphological study of trephinobiopsy specimens from 129 patients with lymphoproliferative and myeloproliferative diseases was carried out over the course of chemotherapy. Combinations of initial and manifest myelofibrosis (loose network of reticulin fibers and extensive network of reticulin and collagen fibers, respectively) predominated at the debut of chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma. Manifest myelofibrosis was detected in patients with chronic myeloid leukemia without hematological response (failure of normalization of hematological values) and in patients with progressing and relapsing multiple myeloma. Combinations of foci of initial and manifest myelofibrosis were most incident in patients with progressing and relapsing chronic lymphoid leukemia. The incidence of myelofibrosis was higher in patients with multiple myeloma and chronic lymphoid leukemia progression and relapses and in patients with chronic myeloid leukemia without hematological response than at the disease debut and in case of response to chemotherapy. The response to chemotherapy in patients with chronic myeloid leukemia and chronic lymphoid leukemia was associated with a decrease in the incidence of myelofibrosis. In patients with multiple myeloma responding to chemotherapy, the incidence of myelofibrosis did not change in comparison with the disease debut.

  15. Compartmentalization of bone morphogenetic proteins and their antagonists in lymphoid progenitors and supporting microenvironments and functional implications

    Science.gov (United States)

    Passa, Ourania; Tsalavos, Sotiris; Belyaev, Nikolai N; Petryk, Anna; Potocnik, Alexandre J; Graf, Daniel

    2011-01-01

    Bone morphogenetic protein (BMP) signalling regulates lymphopoiesis in bone marrow and thymus via the interaction of haemato-lymphoid progenitors with the stroma microenvironment. Despite increasing functional evidence for the role of BMP signalling in lymphopoiesis, little is known of the spatial distribution of BMP/BMP antagonists in the thymus and of how BMP signals exert specific functions in developing lymphocytes. We analysed expression of BMP/BMP antagonists in the thymus and bone marrow and determined the topology of BMP/BMP antagonist expression using lacZ reporter mice. Bmp4, Bmp7, Gremlin and Twisted gastrulation (Twsg1) are all expressed in the thymus and expression was clearly different for each gene investigated. Expression was seen both in cortical and medullary regions suggesting that BMP signals regulate all stages of T-cell development. Two genes in particular, Bmp7 and Twsg1, were dynamically expressed in developing T and B lymphocytes. Their conditional ablation in all haematopoietic cells surprisingly did not affect the steady state of B-cell and T-cell development. This indicates that both lymphoid cell-derived BMP7 and TWSG1 are dispensable for normal lymphopoiesis and that bone-marrow stroma-derived TWSG1 is responsible for the lymphoid defects observed in Twsg1 null mice. In summary our data demonstrate a complex network of lymphoid and stroma derived BMP signals involved in the orchestration of lymphopoiesis in both bone marrow and thymus. PMID:21978004

  16. Virtual endoscopy of the nasopharynx in the evaluation of its normal anatomy and alterations due to lymphoid hyperplasia: preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Pandolfo, Ignazio; Mazziotti, Silvio; Ascenti, Giorgio; Vinci, Sergio; Salamone, Ignazio; Colletti, Giovanni; Blandino, Alfredo [University of Messina, Department of Radiological Sciences, Messina (Italy)

    2004-10-01

    The purpose of this study was to evaluate the diagnostic usefulness of virtual endoscopy in establishing the anatomic appearance of nasopharynx, both normal and affected by lymphoid hyperplasia. Thirty-seven patients affected by chronic rhinosinusal and otomastoid pathology, all studied by rhinoscopy, were examined with multislice computed tomography (CT) and virtual endoscopy of the nasopharynx. Rhinoscopy showed a completely normal nasopharynx in 15 cases and a variable grade of lymphoid hypertrophy in 22 patients. A general agreement was observed between traditional and virtual endoscopy findings in both subgroups. The tasca of Luschka was detected in 13/15 of normal subjects and only in 3/22 patients. The Rosenmuller fossae appeared deeper in normal subjects and their symmetry could be considered an important criterion of normality. In all cases, a good evaluation of the tubaric ostium was obtained. Differentiation between hyperplasic lymphoid tissue and neoplasms is possible only in lymphoid hyperplasia characterized by median crest-like swelling with a narrow base. In most cases, differential diagnosis cannot be based only on morphological criteria of virtual endoscopy, but it should be evaluated considering the overall CT findings and clinical presentation. (orig.)

  17. Gastric LTi cells promote lymphoid follicle formation but are limited by IRAK-M and do not alter microbial growth.

    Science.gov (United States)

    Shiu, J; Piazuelo, M B; Ding, H; Czinn, S J; Drakes, M L; Banerjee, A; Basappa, N; Kobayashi, K S; Fricke, W F; Blanchard, T G

    2015-09-01

    Lymphoid tissue inducer (LTi) cells are activated by accessory cell IL-23, and promote lymphoid tissue genesis and antibacterial peptide production by the mucosal epithelium. We investigated the role of LTi cells in the gastric mucosa in the context of microbial infection. Mice deficient in IRAK-M, a negative regulator of TLR signaling, were investigated for increased LTi cell activity, and antibody mediated LTi cell depletion was used to analyze LTi cell dependent antimicrobial activity. H. pylori infected IRAK-M deficient mice developed increased gastric IL-17 and lymphoid follicles compared to wild type mice. LTi cells were present in naive and infected mice, with increased numbers in IRAK-M deficient mice by two weeks. Helicobacter and Candida infection of LTi cell depleted rag1(-/-) mice demonstrated LTi-dependent increases in calprotectin but not RegIII proteins. However, pathogen and commensal microbiota populations remained unchanged in the presence or absence of LTi cell function. These data demonstrate LTi cells are present in the stomach and promote lymphoid follicle formation in response to infection, but are limited by IRAK-M expression. Additionally, LTi cell mediated antimicrobial peptide production at the gastric epithelium is less efficacious at protecting against microbial pathogens than has been reported for other tissues.

  18. Progress in research on innate lymphoid cells%固有淋巴细胞研究进展

    Institute of Scientific and Technical Information of China (English)

    熊化保; 司传平; 张惠

    2015-01-01

    固有淋巴细胞(innate lymphoid cells ,ILCs)是近年来新发现的一群淋巴细胞,来源于共同淋巴样祖细胞(common lymphoid progenitor ,CLP)。ILCs由多个细胞亚群构成,参与机体抗感染免疫,创伤愈合,组织修复及炎症和肿瘤的发生。本文就ILCs的表型、功能、转录调控以及与疾病的关系作一综述。%Innate lymphoid cells(ILCs) ,identified in recent five years ,are a group of innate lymphocytes .As part of innate immune system ,ILCs arise from a common lymphoid progenitor cells (CLP) .The ILC family include a variety of cell subsets ,which involve in infection immunity ,wound healing ,tissue repair and the development of inflammation and tumor .This article reviews the phenotype ,function ,transcriptional regulation and the role of IL‐Cs in the pathogenesis of disease .

  19. Lymphoid-Tissue-Resident Commensal Bacteria Promote Members of the IL-10 Cytokine Family to Establish Mutualism.

    Science.gov (United States)

    Fung, Thomas C; Bessman, Nicholas J; Hepworth, Matthew R; Kumar, Nitin; Shibata, Naoko; Kobuley, Dmytro; Wang, Kelvin; Ziegler, Carly G K; Goc, Jeremy; Shima, Tatsuichiro; Umesaki, Yoshinori; Sartor, R Balfour; Sullivan, Kaede V; Lawley, Trevor D; Kunisawa, Jun; Kiyono, Hiroshi; Sonnenberg, Gregory F

    2016-03-15

    Physical separation between the mammalian immune system and commensal bacteria is necessary to limit chronic inflammation. However, selective species of commensal bacteria can reside within intestinal lymphoid tissues of healthy mammals. Here, we demonstrate that lymphoid-tissue-resident commensal bacteria (LRC) colonized murine dendritic cells and modulated their cytokine production. In germ-free and antibiotic-treated mice, LRCs colonized intestinal lymphoid tissues and induced multiple members of the IL-10 cytokine family, including dendritic-cell-derived IL-10 and group 3 innate lymphoid cell (ILC3)-derived IL-22. Notably, IL-10 limited the development of pro-inflammatory Th17 cell responses, and IL-22 production enhanced LRC colonization in the steady state. Furthermore, LRC colonization protected mice from lethal intestinal damage in an IL-10-IL-10R-dependent manner. Collectively, our data reveal a unique host-commensal-bacteria dialog whereby selective subsets of commensal bacteria interact with dendritic cells to facilitate tissue-specific responses that are mutually beneficial for both the host and the microbe.

  20. T cell contamination in flow cytometry gating approaches for analysis of innate lymphoid cells.

    Science.gov (United States)

    Burkhard, Sara H; Mair, Florian; Nussbaum, Kathrin; Hasler, Sabrina; Becher, Burkhard

    2014-01-01

    Innate lymphoid cells (ILCs) differ from T and B cells as they do not express genetically rearranged antigen receptors. The most prominent member of this group, NK cells, can be identified by numerous surface receptors such as natural cytotoxicity receptors (NCRs). However, novel groups of ILCs have recently been described and classified based on fate-determining transcription factors and cytokines being produced, similarly to T helper cells. Due to the lack of exclusive markers, ILCs are primarily defined by the paucity of lineage markers. Using RORc-fate-mapping mice, we found that the common lineage exclusion using CD3 yields an ILC population containing a large proportion of T cells with recombined TCR loci and low expression of CD3. Thus, we suggest adding CD5 as a marker for thorough elimination of T cells to avoid erroneous interpretations of ILC function in immunity.

  1. Subcutaneous lymphoid follicular hyperplasia secondary to vaccination: correlation of ultrasound findings with clinical and histological findings.

    Science.gov (United States)

    Castro Copete, M C; Crespo Martínez, C; Martínez García, C; Calbo Maiques, J

    In recent years, the use of vaccines has been standardized within vaccination programs. Adverse effects at the puncture site are usually mild and transient. Nevertheless, in some cases, persistence subcutaneous nodules can develop; these are often underdiagnosed because they are so rare and because of the long time that can transpire between the vaccination and their appearance. Histologically, they consist of a lymphoid follicular hyperplasia that occurs as a reaction to the aluminum particles usually used as an adjuvant in some vaccines. We were unable to find any reference in the radiological literature to these soft-tissue nodules secondary to vaccination. We report the characteristic ultrasound findings that will enable radiologists to identify or strongly suspect these lesions and thereby avoid unnecessary imaging tests that might lead to confusion and inadequate management of these patients. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. [Gastric Mucosa-associated Lymphoid Tissue Lymphoma Based on Outcome of Domestic Treatment].

    Science.gov (United States)

    Jung, Jin Tae

    2016-10-25

    Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection. H. pylori eradication can be performed as a primary therapy regardless of H. pylori status. In Korea, six articles were published about low-grade gastric MALT lymphoma with H. pylori. Complete regression rate after H. pylori eradication is reported at 74.5% to 94.4%. Radiotherapy results in favorable clinical long-term outcomes in patients with early-stage gastric MALT lymphoma who fail H. pylori eradication therapy and those who are H. pylori negative. Chemotherapy could be reserved for patients with metastatic or high-grade lymphoma. In gastric MALT lymphoma, patients with polypoid type on initial endoscopy had a higher likelihood of recurrence than those with diffuse infiltration or ulceration types. The depth of invasion, location of lesions, and chromosomal abnormality with t(11;18) together are predictive factors for failure to remission by H. pylori eradication.

  3. Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Fabian Flores-Borja

    2016-01-01

    Full Text Available Our knowledge and understanding of the tumor microenvironment (TME have been recently expanded with the recognition of the important role of innate lymphoid cells (ILC. Three different groups of ILC have been described based on their ability to produce cytokines that mediate the interactions between innate and adaptive immune cells in a variety of immune responses in infection, allergy, and autoimmunity. However, recent evidence from experimental models and clinical studies has demonstrated that ILC contribute to the mechanisms that generate suppressive or tolerant environments that allow tumor regression or progression. Defining the complex network of interactions and crosstalk of ILC with other immune cells and understanding the specific contributions of each type of ILC leading to tumor development will allow the manipulation of their function and will be important to develop new interventions and therapeutic strategies.

  4. Septic arthritis as the first sign of Candida tropicalis fungaemia in an acute lymphoid leukemia patient

    Directory of Open Access Journals (Sweden)

    Vicari Perla

    2003-01-01

    Full Text Available Fungal infections caused by Candida species have increased in incidence during the past two decades in England, North America and Europe. Candidal arthritis is rare in patients who are not intravenous drug users or are who not using a prostheses. We report the case of a 24-year-old man with acute lymphoid leukemia, who developed Candida tropicalis arthritis during an aplastic period after chemotherapy. This is the eighth case described in the literature of C. tropicalis causing arthritis without intra-articular inoculation. We call attention to an unusual first sign of fungal infection: septic arthritis without intra-articular inoculation. However, this case differs from the other seven, since despite therapy a fast and lethal evolution was observed. We reviewed reported cases, incidence, risk factors, mortality and treatment of neutropenic patients with fungal infections.

  5. Total lymphoid irradiation prevents diabetes mellitus in the Bio-Breeding/Worcester (BB/W) rat

    Energy Technology Data Exchange (ETDEWEB)

    Rossini, A.A.; Slavin, S.; Woda, B.A.; Geisberg, M.; Like, A.A.; Mordes, J.P.

    1984-06-01

    Total lymphoid irradiation (TLI) at doses of 2200 rads or greater prevented diabetes in susceptible BB/W rats. Two of 29 (7%) treated rats became diabetic compared with 23 of 39 (59%) controls. TLI did not, however, prevent insulitis or thyroiditis in nondiabetic rats, nor did it restore the depressed concanavalin-A responsiveness of BB rat lymphocytes. T-lymphocyte subset proportions were the same in both groups. TLI was associated with significant radiation-related mortality, and nondiabetic TLI-treated rats weighed significantly less than controls. It was concluded that TLI is effective in the prevention of BB rat diabetes. However, TLI fails to correct the subclinical immunologic abnormalities of the model and is associated with significant morbidity.

  6. Prostaglandin E₂ constrains systemic inflammation through an innate lymphoid cell-IL-22 axis.

    Science.gov (United States)

    Duffin, Rodger; O'Connor, Richard A; Crittenden, Siobhan; Forster, Thorsten; Yu, Cunjing; Zheng, Xiaozhong; Smyth, Danielle; Robb, Calum T; Rossi, Fiona; Skouras, Christos; Tang, Shaohui; Richards, James; Pellicoro, Antonella; Weller, Richard B; Breyer, Richard M; Mole, Damian J; Iredale, John P; Anderton, Stephen M; Narumiya, Shuh; Maizels, Rick M; Ghazal, Peter; Howie, Sarah E; Rossi, Adriano G; Yao, Chengcan

    2016-03-18

    Systemic inflammation, which results from the massive release of proinflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are not fully understood. We observed that prostaglandin E2 (PGE2), through its receptor EP4, is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treatment with EP4 agonists. Mechanistically, we demonstrate that PGE2-EP4 signaling acts directly on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC-IL-22 axis impairs PGE2-mediated inhibition of systemic inflammation. Hence, the ILC-IL-22 axis is essential in protecting against gut barrier dysfunction, enabling PGE2-EP4 signaling to impede systemic inflammation.

  7. A case of colonic lymphoid tissue invasion by Gymnophalloides seoi in a Korean man

    Science.gov (United States)

    Seo, Min; Chun, Hokyung; Ahn, Geunghwan; Jang, Kee-Taek; Guk, Sang-Mee

    2006-01-01

    A 65-year old Korean man, living in Mokpo-city, Jeollanam-do, Republic of Korea, visited a local clinic complaining of right upper quadrant pain and indigestion. At colonoscopy, he was diagnosed as having a carcinoma of the ascending colon, and thus, a palliative right hemicolectomy was performed. Subsequently, an adult fluke of Gymnophalloides seoi was incidentally found in a surgical pathology specimen of the lymph node around the colon. The worm was found to have invaded gut lymphoid tissue, with characteristic morphologies of a large oral sucker, a small ventral sucker, and a ventral pit surrounded by strong muscle fibers. This is the first reported case of mucosal tissue invasion by G. seoi in the human intestinal tract. PMID:16514288

  8. Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment

    Science.gov (United States)

    Irshad, Sheeba; Gordon, Peter; Wong, Felix; Sheriff, Ibrahim; Tutt, Andrew; Ng, Tony

    2016-01-01

    Our knowledge and understanding of the tumor microenvironment (TME) have been recently expanded with the recognition of the important role of innate lymphoid cells (ILC). Three different groups of ILC have been described based on their ability to produce cytokines that mediate the interactions between innate and adaptive immune cells in a variety of immune responses in infection, allergy, and autoimmunity. However, recent evidence from experimental models and clinical studies has demonstrated that ILC contribute to the mechanisms that generate suppressive or tolerant environments that allow tumor regression or progression. Defining the complex network of interactions and crosstalk of ILC with other immune cells and understanding the specific contributions of each type of ILC leading to tumor development will allow the manipulation of their function and will be important to develop new interventions and therapeutic strategies. PMID:27882334

  9. Interleukin-5-producing group 2 innate lymphoid cells control eosinophilia induced by interleukin-2 therapy.

    Science.gov (United States)

    Van Gool, Frédéric; Molofsky, Ari B; Morar, Malika M; Rosenzwajg, Michelle; Liang, Hong-Erh; Klatzmann, David; Locksley, Richard M; Bluestone, Jeffrey A

    2014-12-04

    Interleukin (IL)-2 promotes regulatory T-cell development and function, and treatment with IL-2 is being tested as therapy for some autoimmune diseases. However, patients receiving IL-2 treatment also experience eosinophilia due to an unknown mechanism. Here, we show that patients receiving low-dose IL-2 have elevated levels of serum IL-5, and this correlates with their degree of eosinophilia. In mice, low-dose IL-2-anti-IL-2 antibody complexes drove group 2 innate lymphoid cells (ILC2) to produce IL-5 and proliferate. Using genetic approaches in mice, we demonstrate that activation of ILC2 was responsible for the eosinophilia observed with IL-2 therapy. These observations reveal a novel cellular network that is activated during IL-2 treatment. A better understanding of the cross talk between these cell populations may lead to more effective targeting of IL-2 to treat autoimmune disease. © 2014 by The American Society of Hematology.

  10. Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells

    Science.gov (United States)

    Astakhova, Lidiia; Ngara, Mtakai; Babich, Olga; Prosekov, Aleksandr; Asyakina, Lyudmila; Dyshlyuk, Lyubov; Midtvedt, Tore; Zhou, Xiaoying; Ernberg, Ingemar; Matskova, Liudmila

    2016-01-01

    The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype. PMID:27441625

  11. Arginase 1 is an innate lymphoid cell-intrinsic metabolic checkpoint controlling type 2 inflammation

    Science.gov (United States)

    Monticelli, Laurel A; Buck, Michael D; Flamar, Anne-Laure; Saenz, Steven A; Wojno, Elia D Tait; Yudanin, Naomi A; Osborne, Lisa C; Hepworth, Matthew R; Tran, Sara V; Rodewald, Hans-Reimer; Shah, Hardik; Cross, Justin R; Diamond, Joshua M; Cantu, Edward; Christie, Jason D; Pearce, Erika L; Artis, David

    2016-01-01

    Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair following activation by cell-extrinsic factors including host-derived cytokines. However, the cell-intrinsic metabolic pathways that control ILC2 function are undefined. Here we demonstrate that expression of the enzyme Arginase 1 (Arg1) is a conserved trait of murine and human ILC2s during acute or chronic lung inflammation. Deletion of murine ILC-intrinsic Arg1 abrogated type 2 lung inflammation by restraining ILC2 proliferation and dampening cytokine production. Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple components of ILC2 metabolic programming by altering arginine catabolism, impairing polyamine biosynthesis and reducing aerobic glycolysis. These data identify Arg1 as a key regulator of ILC2 bioenergetics, controlling proliferative capacity and pro-inflammatory functions that promote type 2 inflammation. PMID:27043409

  12. The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment

    Science.gov (United States)

    King, Bryan; Boccalatte, Francesco; Moran-Crusio, Kelly; Wolf, Elmar; Wang, Jingjing; Kayembe, Clarisse; Lazaris, Charalampos; Yu, Xiaofeng; Aranda-Orgilles, Beatriz; Lasorella, Anna; Aifantis, Iannis

    2016-01-01

    Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. Here we identify the ubiquitin ligase Huwe1 as a crucial regulator of HSC functions via its post-translational control of N-myc. We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid fate specification. Using a novel fluorescent fusion allele (MycnM), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations. N-myc was upregulated in response to stress or upon loss of Huwe1, leading to increased proliferation and stem cell exhaustion. Mycn depletion reversed most of these phenotypes in vivo, suggesting that the attenuation of N-myc by Huwe1 is essential to reestablish homeostasis following stress. PMID:27668798

  13. Type 1 Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells.

    Science.gov (United States)

    Jiao, Yuhao; Huntington, Nicholas D; Belz, Gabrielle T; Seillet, Cyril

    2016-01-01

    Group 1 innate lymphoid cells (ILCs) comprise the natural killer (NK) cells and ILC1s that reside within peripheral tissues. Several different ILC1 subsets have recently been characterized; however, no unique markers have been identified that uniquely define these subsets. Whether ILC1s and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILCs and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body. This raises the question of whether each of these populations mediate distinct functions during infection and tumor immunosurveillance. Here, we review the diversity of the Group 1 ILC subsets in their transcriptional regulation, localization, mobility, and receptor expression, and highlight the challenges in unraveling the individual functions of these different populations of cells.

  14. Simultaneous Occurrence of Early Gastric Carcinoma and Mucosa-Associated Lymphoid Tissue Lymphoma of the Omentum

    Directory of Open Access Journals (Sweden)

    Tomohiro Murakami

    2014-03-01

    Full Text Available The simultaneous association of gastric carcinoma with omental mucosa-associated lymphoid tissue (MALT lymphoma is a rare event that has not been reported previously. We focused on the hypothetic pathogenetic mechanisms, diagnosis and treatment of this rare condition. A 55-year-old woman with Helicobacter pylori infection underwent distal gastrectomy in our hospital. Three independent early gastric cancers and a mass near the cecum were diagnosed preoperatively. Pathological review of the resected stomach showed three independent early signet ring cell gastric carcinomas, and the mass in the omentum near the cecum was shown to be omental MALT lymphoma. Due to the nature of the patient's disease, she was started on medical eradication of H. pylori. Synchronous gastric adenocarcinoma and omental MALT lymphoma is a rare event. Special attention given to H. pylori-associated gastric cancer patients can avoid misdiagnosis and lead to adequate treatment.

  15. Cutting Edge: Innate Lymphoid Cells Suppress Homeostatic T Cell Expansion in Neonatal Mice.

    Science.gov (United States)

    Bank, Ute; Deiser, Katrin; Finke, Daniela; Hämmerling, Günter J; Arnold, Bernd; Schüler, Thomas

    2016-05-01

    In adult mice, lymphopenia-induced proliferation (LIP) leads to T cell activation, memory differentiation, tissue destruction, and a loss of TCR diversity. Neonatal mice are lymphopenic within the first week of life. This enables some recent thymic emigrants to undergo LIP and convert into long-lived memory T cells. Surprisingly, however, most neonatal T cells do not undergo LIP. We therefore asked whether neonate-specific mechanisms prevent lymphopenia-driven T cell activation. In this study, we show that IL-7R-dependent innate lymphoid cells (ILCs) block LIP of CD8(+) T cells in neonatal but not adult mice. Importantly, CD8(+) T cell responses against a foreign Ag are not inhibited by neonatal ILCs. This ILC-based inhibition of LIP ensures the generation of a diverse naive T cell pool in lymphopenic neonates that is mandatory for the maintenance of T cell homeostasis and immunological self-tolerance later in life.

  16. Stepping stones in the path of glucocorticoid-driven apoptosis of lymphoid cells

    Institute of Scientific and Technical Information of China (English)

    E.Brad Thompson

    2008-01-01

    Cumulative work on glucocorticoid (GC) regulation of genes in lymphoid cell cultures has revealed that apoptotic sensitivity to GCs depends on sufficient active GC receptors in the cells.The actions of the ligand-driven GC receptor that lead to apoptosis depend on interactions with other major cell.signaling systems,including the MAPK pathways,the cA P/PKA pathway,the hedgehogpathway,the mTORsystem and the c-myc system.The balance between these systems determines whether a given cell responds to GCs by undergoing apoptosis.A central core of networked genes may be found under GC control in many types of malignant,GCsensitive cells.The partial core list identified should be tested in clinical cell samples from hematologic malignancies.

  17. Group 2 innate lymphoid cells license dendritic cells to potentiate memory TH2 cell responses.

    Science.gov (United States)

    Halim, Timotheus Y F; Hwang, You Yi; Scanlon, Seth T; Zaghouani, Habib; Garbi, Natalio; Fallon, Padraic G; McKenzie, Andrew N J

    2016-01-01

    Rapid activation of memory CD4(+) T helper 2 (TH2) cells during allergic inflammation requires their recruitment into the affected tissue. Here we demonstrate that group 2 innate lymphoid (ILC2) cells have a crucial role in memory TH2 cell responses, with targeted depletion of ILC2 cells profoundly impairing TH2 cell localization to the lungs and skin of sensitized mice after allergen re-challenge. ILC2-derived interleukin 13 (IL-13) is critical for eliciting production of the TH2 cell-attracting chemokine CCL17 by IRF4(+)CD11b(+)CD103(-) dendritic cells (DCs). Consequently, the sentinel function of DCs is contingent on ILC2 cells for the generation of an efficient memory TH2 cell response. These results elucidate a key innate mechanism in the regulation of the immune memory response to allergens.

  18. The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing.

    Science.gov (United States)

    Björklund, Åsa K; Forkel, Marianne; Picelli, Simone; Konya, Viktoria; Theorell, Jakob; Friberg, Danielle; Sandberg, Rickard; Mjösberg, Jenny

    2016-04-01

    Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system.

  19. IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing.

    Science.gov (United States)

    Rak, Gregory D; Osborne, Lisa C; Siracusa, Mark C; Kim, Brian S; Wang, Kelvin; Bayat, Ardeshir; Artis, David; Volk, Susan W

    2016-02-01

    Breaches in the skin barrier initiate an inflammatory immune response that is critical for successful wound healing. Innate lymphoid cells (ILCs) are a recently identified population of immune cells that reside at epithelial barrier surfaces such as the skin, lung, and gut, and promote proinflammatory or epithelial repair functions after exposure to allergens, pathogens, or chemical irritants. However, the potential role of ILCs in regulating cutaneous wound healing remains undefined. Here, we demonstrate that cutaneous injury promotes an IL-33-dependent group 2 ILC (ILC2) response and that abrogation of this response impairs re-epithelialization and efficient wound closure. In addition, we provide evidence suggesting that an analogous ILC2 response is operational in acute wounds of human skin. Together, these results indicate that IL-33-responsive ILC2s are an important link between the cutaneous epithelium and the immune system, acting to promote the restoration of skin integrity after injury.

  20. Total lymphoid irradiation therapy in refractory rheumatoid arthritis. Fifteen- to forty-month followup

    Energy Technology Data Exchange (ETDEWEB)

    Brahn, E.; Helfgott, S.M.; Belli, J.A.; Anderson, R.J.; Reinherz, E.L.; Schlossman, S.F.; Austen, K.F.; Trentham, D.E.

    1984-05-01

    Twelve patients with refractory rheumatoid arthritis were treated with total lymphoid irradiation (TLI) to a total cumulative dose of 3,000 rads. Post-TLI morbidity/mortality included 8 patients with xerostomia, 4 with weight loss of greater than 10 kg, 3 with loss of 4 or more teeth, 3 with herpes zoster, 4 with bacterial infection that was fatal in 2, 3 with hypothyroidism, 1 with cutaneous vasculitis, and death from myocardial infarction in 1 patient and cardiorespiratory arrest in another. Ten of the patients were reevaluated 15-40 months (mean +/- SE, 30 +/- 2) after completion of TLI, and significant improvement was noted in several disease parameters including number of swollen joints, duration of morning stiffness, and 50-foot walking time. Blood lymphopenia and a decrease in helper T cells (T4) were also noted. These data suggest that changes in immunoregulation induced by TLI can produce longlasting alterations in rheumatoid arthritis, although adverse effects may limit its efficacy.

  1. Sjogren syndrome complicated by mucosa-associated lymphoid tissue lymphoma and lymphocytic interstitial pneumonia

    Directory of Open Access Journals (Sweden)

    Fatma eAhmed

    2015-08-01

    Full Text Available Sjogren Syndrome (SS is an autoimmune disease with exocrine glands dysfunction and multiorgan involvement. It is associated with increased risk of lymphoproliferative disorders, especially B-cell marginal zone lymphoma. While the role of F-18 Flurodoxyglucose position emission tomography/CT (F-18 FDG PET/CT for evaluation of lymphoma has been established, its use in patients with a chronic history of SS to evaluate for possible lymphoproliferative disorders or multiorgan involvement is limited. We present a case of chronic SS in which F-18 FDG PET/CT demonstrated FDG avid intraparotid and cervical lymph nodes pathologically proven to be Mucosa-associated lymphoid tissue (MALT lymphoma. In addition, the patient had bibasilar cystic changes consistent with lymphocytic interstitial pneumonia (LIP.

  2. Kidney allograft tolerance in diabetic patients after total lymphoid irradiation (TLI)

    Energy Technology Data Exchange (ETDEWEB)

    Ang, K.K.; Vanrenterighem, Y.; Waer, M.; Michielsen, P.; Schueren, E. van der (University Hospital St. Rafael, Leuven (Belgium)); Vandeputte, M. (Louvain Univ. (Belgium). Rega Institute for Medical Research)

    1985-04-01

    The value of total lymphoid irradiation (TLI) combined with low dose prednisone as sole immunosuppressive regimen in renal allograft transplantation in humans has been investigated. Seventeen patients with end-stage diabetic nephropathy received TLI to a cumulative dose of 20-30 Gy in fractions of 1 Gy. Cadaver kidneys were grafted as soon as they were available after completion of TLI. Profound and long-term immunosuppression has been achieved in 17 patients. Six patients live already more than one year and 7 for less than one year with a functioning kidney graft. One patient returned to chronic hemodialysis 11 months after transplantation and died of pericardial tamponade one month later. One patient had severe acute rejection for which cyclosporine A was administered; he died of septic shock as a consequence of immune deficiency a month later. The other two patients succumbed to other causes (myocardial infarction and hyperglycemia).

  3. Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin

    DEFF Research Database (Denmark)

    Dyring-Andersen, B; Geisler, Carsten; Agerbeck, C

    2014-01-01

    patients with psoriasis compared with healthy skin and skin from patients with contact allergy to nickel. Furthermore, skin ILCs expressed high levels of the natural killer receptor NKG2D. NKG2D binds to stress-induced ligands, including major histocompatibility complex class I-related chain A, which we......BACKGROUND: Psoriasis is a common immune-mediated inflammatory disease that affects the skin and joints. The interleukin (IL)-23/IL-17A axis and IL-22 play key roles in the pathogenesis of psoriasis. IL-23-responsive innate lymphoid cells (ILCs) with a high capacity to produce IL-17 and/or IL-22....... METHODS: Skin biopsies were taken from healthy skin, nonlesional and lesional psoriatic skin, and nickel- and petrolatum-exposed skin from patients with contact allergy to nickel, and lymphocytes were isolated. The cells were stained and characterized by flow cytometry. Cytokine and ligand mRNA expression...

  4. Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Kazuhiko (Yamato Seiwa Hospital, Kanagawa (Japan)); Rapaport, F.T.

    1992-12-01

    With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author).

  5. Executive Dysfunction 25 Years after Treatment with Cranial Radiotherapy for Pediatric Lymphoid Malignancies.

    Science.gov (United States)

    Schuitema, Ilse; de Sonneville, Leo; Kaspers, Gertjan; van der Pal, Helena; Uyttebroeck, Anne; van den Bos, Cor; Veerman, Anjo

    2015-10-01

    The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are now aging into adulthood, and concerns are growing about the development of radiotherapy-induced cognitive deficits in the aging brain. These deficits are hypothesized to increase over time. Their impact on daily functioning of older survivors, and the accompanying need for interventions, should be anticipated. By describing a detailed profile of executive function deficits and their associations with age, specific targets for neuropsychological intervention can be identified. Fifty survivors of childhood lymphoid malignancies and 58 related controls were assessed with the Amsterdam Neuropsychological Tasks program. The survivors were on average 31.1 (4.9) years old, treated with 22.5 (6.8) Gy cranial irradiation, and examined on average 25.5 (3.1) years after diagnosis. The survivors showed significantly decreased response speed, irrespective of the task at hand. Furthermore, we found deficits in working memory capacity, inhibition, cognitive flexibility, executive visuomotor control, attentional fluctuations, and sustained attention. Older age was associated with poorer performance on executive visuomotor control and inhibition. On executive visuomotor control, 50% of female survivors performed more than 1.5 SD below average, versus 15.4% of male survivors. The combination of visuospatial working memory problems and decreasing executive visuomotor control could result in difficulty with learning new motor skills at older ages, like walking with a cane. Deterioration of executive control and inhibition may result in decreased behavioral and emotional regulation in aging survivors. Especially the deficiency in executive visuomotor control in female survivors should be considered for (prophylactic) intervention.

  6. Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus.

    Science.gov (United States)

    De Groof, Aurélie; Hémon, Patrice; Mignen, Olivier; Pers, Jacques-Olivier; Wakeland, Edward K; Renaudineau, Yves; Lauwerys, Bernard R

    2017-05-13

    Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic mice), and how they integrate in our present understanding of the pathogenesis of the disease. In particular, we focus on (autoreactive) T cell activation patterns in lupus-prone mice. Break of T cell tolerance to chromatin constituents (histone peptides) is key to the development of the disease and is related to T cell intrinsic defects, contributed by genetic susceptibility factors and by extrinsic amplificatory mechanisms, in particular over-stimulation by antigen-presenting cells. We also describe shifts in B cell sub-populations, going from skewed immature B cell populations as an indication of disturbed central and peripheral tolerance checkpoints, to enriched long-lived plasma cells, which are key to persistent autoantibody production in the disease. B cell activation mechanisms in SLE are both T cell-dependent (break of tolerance and production of specific autoantibodies) and -independent (polyclonal B cell activation, production of autoantibodies by long-lived plasma cells). By providing a comprehensive evaluation of B and T cell surface markers in two major mouse models of SLE and a description of their changes before and after disease onset, this review illustrates how the study of lymphoid cell phenotype delivers key information regarding pathogenic pathways and supplies tools to assess the beneficial effects of novel therapeutic interventions.

  7. Increased risk of lymphoid neoplasms in patients with Philadelphia chromosome-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Vannucchi, Alessandro M; Masala, Giovanna; Antonioli, Elisabetta; Chiara Susini, Maria; Guglielmelli, Paola; Pieri, Lisa; Maggi, Laura; Caini, Saverio; Palli, Domenico; Bogani, Costanza; Ponziani, Vanessa; Pancrazzi, Alessandro; Annunziato, Francesco; Bosi, Alberto

    2009-07-01

    Association of myeloproliferative neoplasm (MPN) with lymphoproliferative neoplasm (LPN) has been occasionally reported. The aim of this study, which included 353 patients with polycythemia vera and 467 with essential thrombocythemia, was to assess whether the risk of developing LPN is increased in MPN patients. Expected numbers of LPN incident cases were calculated based on 5-year age group, gender, and calendar time-specific cancer incidence rates in the general population of the same area. Standardized incidence ratios were computed to estimate the relative risk of developing LPN. Analyses were carried out for the whole series and then separately for essential thrombocythemia and polycythemia vera, gender, and JAK2V617F genotype. With 4,421 person-years, we found 11 patients developing LPN, including four chronic lymphocytic leukemias, five non-Hodgkin's lymphomas, and two plasma cell disorders, after a median interval time of 68 months from MPN diagnosis. Cumulative risk to develop LPN at 5 and 10 years was 0.93% (95% confidence interval, 0.39-2.22) and 2.96% (95% confidence interval, 1.52-5.72), respectively. There was a 3.44-fold increased risk of LPN compared with the general population, ranging from 2.86 for plasma cell disorder to 12.42 for chronic lymphocytic leukemia; the risk was significantly increased in JAK2V617F mutated patients (5.46-fold) and in males (4.52-fold). The JAK2V617F mutation was found in lymphoid tumor cells in two of three cases evaluated, indicating that, in some patients, LPN originated in a JAK2V617F mutated common lymphoid-myeloid hematopoietic progenitor cell. We conclude that the risk of developing LPN is significantly increased in MPN patients compared with the general population.

  8. Lymphoid Hyperplasia of the Appendix: A Potential Pitfall in the Sonographic Diagnosis of Appendicitis.

    Science.gov (United States)

    Xu, Yingding; Jeffrey, R Brooke; DiMaio, Michael A; Olcott, Eric W

    2016-01-01

    The objective of this study was to test the hypothesis that thickening of the lamina propria, a finding produced by lymphoid hyperplasia, is significantly associated with false-positive sonographic diagnoses of appendicitis in 6- to 8-mm noncompressible appendixes. Sonograms of 119 consecutive patients with suspected appendicitis and 6- to 8-mm noncompressible appendixes were retrospectively blindly evaluated for thickening of the lamina propria (short axis thickness ≥ 1 mm). The reference standard for appendicitis was pathologic analysis of resected specimens. Results were compared with the two-tailed Fisher exact test. Thirty-one patients (26.1%) had a thickened lamina propria and 88 (73.9%) did not. Of the 27 pediatric patients with a thickened lamina propria, five (18.5%) had true-positive and 22 (81.5%) had false-positive sonograms for appendicitis; among the 55 pediatric patients without a thickened lamina propria, 27 (49.1%) had true-positive and 28 (50.9%) had false-positive sonograms for appendicitis (p = 0.009). Similar differences in adult patients were not statistically significant. All five pediatric patients with appendicitis and thickened lamina propria also showed two or more findings of periappendiceal fluid, hyperechoic periappendiceal fat, or mural hyperemia on color Doppler examination, compared with two of 22 similar pediatric patients without appendicitis (p hyperplasia may result in a noncompressible appendix 6-8 mm in diameter and may be misdiagnosed as appendicitis in pediatric patients. True-positive diagnoses of appendicitis can be accurately identified by the presence of at least two additional findings from the group of periappendiceal fluid, hyperechoic periappendiceal fat, and mural hyperemia. Identifying the characteristic sonographic appearance of lymphoid hyperplasia may help prevent false-positive misdiagnoses of appendicitis.

  9. Distribution pattern of bovine viral diarrhoea virus type 1 genome in lymphoid tissues of experimentally infected sheep.

    Science.gov (United States)

    Karikalan, M; Rajukumar, K; Mishra, N; Kumar, M; Kalaiyarasu, S; Rajesh, K; Gavade, V; Behera, S P; Dubey, S C

    2016-06-01

    In this study, cellular localization and the distribution pattern of BVDV genome in lymphoid tissues during the course of experimental acute BVDV-1 infection of sheep was investigated. Tonsils, mesenteric lymph nodes (MLN) and spleen were collected on 3, 6, 9, 12 and 15 days post infection (dpi) from twenty 4-month-old lambs, experimentally inoculated intra-nasally with 5 × 10(5) TCID50 of a non-cytopathic (ncp) BVDV-1 isolate, Ind-17555. Tissues collected from ten mock-infected lambs served as controls. In situ hybridization (ISH) was carried out in paraformaldehyde fixed paraffin embedded tissue sections using digoxigenin labelled riboprobe targeting 5'-UTR of BVDV-1. BVDV genome was detected at all the intervals from 3 dpi to 15 dpi in the lymphoid tissues with variations between the intervals and also amongst the infected sheep. During the early phase of acute infection, presence of viral genome was more in tonsils than MLN and spleen, whereas the distribution was higher in MLN during later stages. BVDV-1 genome positive cells included lymphocytes, macrophages, plasma cells, reticular cells and sometimes crypt epithelial cells. Genome distribution was frequently observed in the lymphoid follicles of tonsils, MLN and spleen, besides the crypt epithelium in tonsils, paracortex and medullary sinus and cords of MLN. Most abundant and widespread distribution of BVDV-1 genome was observed on 6 dpi while there was a reduction in number and intensity of positive signals by 15 dpi in most of the infected animals. This is the first attempt made to study the localisation of BVDV-1 in lymphoid tissues of acutely infected sheep by in situ hybridization. The results show that the kinetics of BVDV-1 distribution in lymphoid tissues of experimentally infected non-pregnant sheep follows almost a similar pattern to that demonstrated in BVDV infected cattle.

  10. Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies.

    Science.gov (United States)

    Iwata, Hiroshi; Matsuo, Keitaro; Hara, Shigeo; Takeuchi, Kengo; Aoyama, Tomonori; Murashige, Naoko; Kanda, Yoshinobu; Mori, Shin-Ichiro; Suzuki, Risturo; Tachibana, Shintaro; Yamane, Masaaki; Odawara, Masato; Mutou, Yoshitomo; Kami, Masahiro

    2006-02-01

    It has been speculated that the use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors (statins) is associated with the risk of malignant diseases. Considering their immunosuppressive activities, malignant diseases that are associated with an immunosuppressive status seem feasible to examine the association. We therefore examined the association between statin use and development of lymphoid malignancies in a case-control study. Cases were 221 consecutive incident cases with histopathologically proven lymphoid malignancies (lymphoma and myeloma), hospitalized in the Department of Hematology of Toranomon Hospital (Tokyo, Japan) between 1995 and 2001. Two independent control groups, comprising 442 and 437 inpatients without malignancies from the Departments of Orthopedics and Otorhinolaryngology of the same hospital, were selected to test for consistency of association. Controls were matched individually with cases for age, sex and year of admission. Subject information, including statin use, was abstracted from medical records at the time of hospitalization. Strength of association was evaluated as an adjusted odds ratios (aOR) using a conditional logistic regression model. A higher frequency of statin use was found among patients with lymphoid malignancies in comparison with both orthopedic (aOR 2.11, 95% CI 1.20-3.69, P = 0.009) and otorhinolaryngology patients (aOR 2.59, 95% CI 1.45-4.65, P = 0.001), the significance being maintained when the two control groups were combined (aOR 2.24, 95% CI 1.37-3.66, P = 0.001). In conclusion, we observed an elevated risk of lymphoid malignancy with statin use among Japanese patients. Further evaluations in different populations are required to draw conclusions as to the carcinogenicity of lymphoid malignancies with statin use.

  11. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells.

    Science.gov (United States)

    Moro, Kazuyo; Yamada, Taketo; Tanabe, Masanobu; Takeuchi, Tsutomu; Ikawa, Tomokatsu; Kawamoto, Hiroshi; Furusawa, Jun-Ichi; Ohtani, Masashi; Fujii, Hideki; Koyasu, Shigeo

    2010-01-28

    Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors and lymphoid tissue inducer cells. These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells. Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection. After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.

  12. Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

    1985-01-01

    The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae.

  13. The tryptophan derivative, tranilast, and conditioned medium with indoleamine 2,3-dioxygenase-expressing cells inhibit the proliferation of lymphoid malignancies.

    Science.gov (United States)

    Suwa, Shihoko; Kasubata, Aya; Kato, Miyu; Iida, Megumi; Watanabe, Ken; Miura, Osamu; Fukuda, Tetsuya

    2015-03-01

    Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan degradation and induces immunosuppression. Although IDO is an important factor that allows tumors to escape from immunological attack, its effect on lymphoid malignancies has not been fully revealed. We evaluated the expression of IDO in samples from patients with B-cell malignancies. The IDO expression in the tumor samples was comparable to those in peripheral blood mononuclear cells from healthy donors and had mainly originated from non-B cell populations. We introduced IDO gene into Chinese hamster ovary (CHO) cells. We then cultured various cell lines using CHO- or CHO-IDO-conditioned medium. Compared with the CHO medium (CHO-CM), the CHO-IDO medium (IDO-CM) decreased the viability of lymphoid cell lines but not those of the non-lymphoid lines. Next, we examined the effects of tryptophan metabolites on lymphoid tumors, and revealed that the drug N-[3',4'-dimethoxycinnamoyl] anthranilic acid (tranilast), a synthetic derivative of the tryptophan metabolite, was able to repress proliferation and dose-dependently induce cell death of lymphoid cell lines. Tranilast induced the activation of the c-Jun N-terminal kinase, which is activated by cellular stress, in lymphoid cells. The effect of tranilast on lymphoid cells was independent of the aryl hydrocarbon receptor (AhR) although tranilast has been reported to be an AhR agonist. Finally, the administration of tranilast decreased murine lymphoid tumor progression in vivo. These results indicated that IDO and tryptophan derivatives, particularly tranilast, can be tools for the therapy for lymphoid malignancies.

  14. New Players in the Same Old Game: Disturbance of Group 2 Innate Lymphoid Cells in HIV-1 and Mycobacterium leprae Co-infected Patients

    Science.gov (United States)

    Papotto, Pedro Henrique; Maeda, Solange; Tomimori, Jane; Xavier, Marília Brasil; Rizzo, Luiz Vicente; Kallas, Esper Georges; Carvalho, Karina Inácio

    2015-01-01

    Abstract Leprosy control is achieved through a fine-tuning of TH1 and TH2 immune response pattern balance. Given the increasing epidemiological overlay of HIV and M. leprae infections, immune response in co-infected patients consists in an important contemporary issue. Here we describe for the first time the innate lymphoid cells compartment in peripheral blood of leprosy and HIV/M. leprae co-infected patients, and show that co-infection increases group 2 innate lymphoid whilst decreasing group 1 innate lymphoid cells frequencies and function. PMID:26335023

  15. ACTIVATION MECHANISMS OF GUT-ASSOCIATED LYMPHOID TISSUE UNDER CHRONIC SOCIAL STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    A. M. Kamyshnyi

    2015-01-01

    Full Text Available Stress-induced immune disregulation is a risk factor of autoimmune and inflammatory diseases, but, so far, the mechanisms for this effect are not fully known. Expression levels of specific mRNAs were assessed in gut-associated lymphoid tissue (GALT from Wistar rats subjected to chronic social stress (CSS. Gene expression was evaluated for NR3C1, Adrβ2, as well as IL-1β, IL-17α pro-inflammatory cytokines, and Nlrp, an inflammasome gene. Under the CSS conditions, we have shown altered distribution of RORγt +, FoxP3+, LMP2+, XBP1+ lymphocytes in GALT.The experiments were carried out with female Wistar rats aged 5–6 months. Specific mRNA expression for the target genes was determined by means of real-time PCR performed in a CFX96™ thermocycler («BioRadLaboratories, Inc»,USA. Relative levels of a target gene expression were quantified by the ΔΔCt method, being compared with rat GAPDH reference gene expression. Statistical analysis was performed with available «BioRad СFX Manager 3.1» software. Specific monoclonal rat antibodes were used for detection of immunopositive lymphocytes by means of indirect immunofluorescence technique.CSS development leads to decreased levels of mRNA expression for Nr3c1 and Adrβ2-genes in the GALT cells, being accompanied with unidirectional changes, i.e., increased transcription of pro-inflammatory cytokine mRNAs (IL-1β, IL-17α and Nlrp3-inflammasome genes. These changes are accompanied by decreased FoxP3+/RORγt + cell ratio and predominant Th17 differentiation accompanied by suppressor failure. In addition, CSS development was characterized by unidirectional tendency for increasing total number of LMP2+ lymphocytes and reduced ХВР1+ cell population density in lymphoid structures of rat ileum.The events observed in GALT cell populations under CSS conditions are opposing classical paradigm of the stress response. The CSS-associated effects do not promote immunosuppression, however, are able to cause

  16. Lymphoid tumors of Xenopus laevis with different capacities for growth in larvae and adults.

    Science.gov (United States)

    Robert, J; Guiet, C; Du Pasquier, L

    1994-01-01

    Three new lymphoid tumors offering an assortment of variants in terms of MHC class I expressions, MHC class II expression, and Ig gene transcription have been discovered in the amphibian Xenopus. One was developed in an individual of the isogenic LG15 clone (LG15/0), one in a frog of the LG15/40 clone (derived from a small egg recombinant of LG15), and one (ff-2) in a male ff sib of the individual in which MAR1, the first lymphoid tumor in Xenopus was found 2 years ago. These tumors developed primarily as thymus outgrowths and were transplantable in histocompatible tadpoles but not in nonhistocompatible hosts. Whereas LG15/0 and LG15/40 tumor cells also grow in adult LG15 frogs, the ff-2 tumor, like the MAR1 cell line, is rejected by adult ff animals. Using flow cytometry with fluorescence-labeled antibodies and immunoprecipitation analysis, we could demonstrate that, like MAR1, these three new tumors express on their cell surface lymphopoietic markers recognized by mAbs F1F6 and RC47, as well as T-cell lineage markers recognized by mAbs AM22 (CD8-like) and X21.2, but not by immunologobulin (Ig) nor MHC class II molecules. Another lymphocyte-specific marker AM15 is expressed by 15/0 and 15/40 but not ff-2 tumor cells. The ff-2 tumor cell expresses MHC class I molecule in association with beta 2-microglobulin on the surface, 15/40 cells contain cytoplasmic class I alpha chain that is barely detected at the cell surface by fluocytometry, and 15/0 cells do not synthesize class I alpha chain at all. The three new tumors all produce large amounts of IgM mRNA of two different sizes but no Ig protein on the membrane nor in the cytoplasm. All tumor cell types synthesize large amount of Myc mRNA and MHC class I-like transcripts considered to be non classical.

  17. Role of group 3 innate lymphoid cells during experimental otitis media in a rat model.

    Science.gov (United States)

    Cho, Chang Gun; Gong, Sung Ho; Kim, Hee-Bok; Song, Jae-Jun; Park, Joo Hyun; Lim, Yun-Sung; Park, Seok-Won

    2016-09-01

    The objective of this study was to evaluate the role of group 3 innate lymphoid cells (ILC3) in the middle ear (ME) mucosal response to bacterial infection in a rat model. To confirm the role of ILC3 in bacterially induced otitis media (OM), the serum concentrations of IL-17 and IL-22 were determined by ELISA, and the tissue expression of IL-17 and IL-22 in infected ME mucosa was assessed by immunohistochemical staining. Immunohistochemical staining of specific cell surface markers was also assessed to confirm the origin of the cells expressing IL-17 and IL-22. Twenty Sprague-Dawley rats were used in the surgically-induced animal model of OM. OM was induced by inoculation of non-typeable Haemophilus influenzae into the ME cavity of the rats. The rats were divided into four experimental groups: three infected groups and one control group. Infected groups were subdivided into sets of 5 rats, one for each of the three time points (1, 4 and 7 days post-inoculation). For determination of rat IL-17 and IL-22 levels in infected rats and control rats, infected or control ME mucosa sections were analyzed by immunohistochemistry with specific antibodies directed against IL-17 and IL-22. Immunohistochemical staining for CD3, RORγt, and NKp46 were also conducted on the samples to confirm the origin of cells expressing IL-17 and IL-22. IL-17 and IL-22 serum concentrations were significantly increased in the infected rats compared to control rats. Immunohistochemical staining revealed increased IL-17 and IL-22 expressions in all infected ME mucosae from the first day after inoculation. In addition, the results of tissue staining for the specific surface markers were negative for CD3 and NKp46, but were highly positive for RORγt. IL-17 and IL-22 revealed their association with the bacterially induced proliferative and hyperplastic responses of ME mucosa, which are characteristic features in pathogenesis of OM. Surface marker examination showed that the source cells for IL-17

  18. Diffuse duodenal nodular lymphoid hyperplasia: a large cohort of patients etiologically related to Helicobacter pylori infection

    Science.gov (United States)

    2011-01-01

    Background Nodular lymphoid hyperplasia of gastrointestinal tract is a rare disorder, often associated with immunodeficiency syndromes. There are no published reports of its association with Helicobacter pylori infection. Methods From March 2005 till February 2010, we prospectively followed all patients with diffuse duodenal nodular lymphoid hyperplasia (DDNLH). Patients underwent esophagogastroduodenoscopy with targeted biopsies, colonoscopy, and small bowel video capsule endoscopy. Duodenal nodular lesions were graded from 0 to 4 based on their size and density. Patients were screened for celiac sprue (IgA endomysial antibody), immunoglobulin abnormalities (immunoglobulin levels & serum protein electrophoresis), small intestine bacterial overgrowth (lactulose hydrogen breath test), and Helicobacter pylori infection (rapid urease test, and histological examination of gastric biopsies). Patients infected with Helicobacter pylori received sequential antibiotic therapy and eradication of infection was evaluated by 14C urea breath test. Follow up duodenoscopies with biopsies were performed to ascertain resolution of nodular lesions. Results Forty patients (Males 23, females 17; mean age ± 1SD 35.6 ± 14.6 years) with DDNLH were studied. Patients presented with epigastric pain, vomiting, and weight loss. Esophagogastroduodenoscopy showed diffuse nodular lesions (size varying from 2 to 5 mm or more) of varying grades (mean score ± 1SD 2.70 ± 0.84) involving postbulbar duodenum. Video capsule endoscopies revealed nodular disease exclusively limited to duodenum. None of the patients had immunoglobulin deficiency or small intestine bacterial overgrowth or positive IgA endomysial antibodies. All patients were infected with Helicobacter pylori infection. Sequential antibiotic therapy eradicated Helicobacter pylori infection in 26 patients. Follow up duodenoscopies in these patients showed significant reduction of duodenal nodular lesions score (2.69 ± 0.79 to 1.50 ± 1

  19. Replication of an Association Between the Lymphoid Tyrosine Phosphatase Locus (LYP/PTPN22) With Type 1 Diabetes, and Evidence for Its Role as a General Autoimmunity Locus

    National Research Council Canada - National Science Library

    Deborah Smyth; Jason D. Cooper; Joanne E. Collins; Joanne M. Heward; Jayne A. Franklyn; Joanna M.M. Howson; Adrian Vella; Sarah Nutland; Helen E. Rance; Lisa Maier; Bryan J. Barratt; Cristian Guja; Constantin Ionescu-Tı̂rgovişte; David A. Savage; David B. Dunger; Barry Widmer; David P. Strachan; Susan M. Ring; Neil Walker; David G. Clayton; Rebecca C.J. Twells; Stephen C.L. Gough; John A. Todd

    2004-01-01

    Replication of an Association Between the Lymphoid Tyrosine Phosphatase Locus ( LYP/PTPN22 ) With Type 1 Diabetes, and Evidence for Its Role as a General Autoimmunity Locus Deborah Smyth 1 , Jason D...

  20. Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Terr, A.I.; Moss, R.B.; Strober, S.

    1987-12-01

    Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer T cells does not appear to influence preexisting levels of IgE antibodies.

  1. Primary thymic mucosa-associated lymphoid tissue lymphoma with multiple thin walled lung cysts: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Lung-Yun Kang; Szu-Pei Ho; Yi-Pin Chou

    2013-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma of the thymus is rare.We reported a case of a 37-year-old Chinese female with Sj(o)gren's syndrome and hyperglobulinemia.She suffered from chronic cough for 3 weeks.Chest computed tomography (CT) demonstrated a multiloculated cystic mass in mediastinum prevascular space and multiple lung cysts.Laboratory exam of autoimmune markers showed positive of antinuclear antibody (ANA),Sj(o)gren's syndrome A (SSA),Sj(o)gren's syndrome B (SSB),and rheumatoid factors (RF).Thymectomy with lymph node dissection was performed.The pathology report revealed thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.Under immunohistochemical stains,CD20 and Bcl-2 were positive.No evidence of recurrence of disease was found.

  2. Primary gastric T cell lymphoma mimicking marginal zone B cell lymphoma of mucosa-associated lymphoid tissue.

    Science.gov (United States)

    Holanda, Danniele; Zhao, Merry Y; Rapoport, Aaron P; Garofalo, Michael; Chen, Qing; Zhao, X Frank

    2008-07-01

    Primary gastric T cell lymphoma is rare and mostly of large cell type. In this paper, we present a case of gastric T cell lymphoma morphologically similar to the gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Morphologically, the cells are small with abundant clear cytoplasm. Lymphoepithelial lesions are readily identified with diffuse destruction of gastric glands. Immunohistochemically, the neoplastic cells are CD3+/CD4+/CD8-/Granzyme B-. Molecular studies revealed monoclonal T cell receptor gamma gene rearrangement. Clinically, the patient responded initially to four cycles of R-CHOP, but then progressed. Because peripheral T cell lymphoma is usually associated with a poor prognosis, whereas marginal zone B cell lymphoma is an indolent lymphoproliferative disorder, this morphologic mimicry should be recognized and completely investigated when atypical small lymphoid infiltrates with lymphoepithelial lesions are encountered in the stomach.

  3. Role of murine intestinal interleukin-1 receptor 1-expressing lymphoid tissue inducer-like cells in Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Vincent L Chen

    Full Text Available Interleukin (IL-1 signaling plays a critical role in intestinal immunology. Here, we report that the major population of intestinal lamina propria lymphocytes expressing IL-1 receptor 1 (IL-1R1 is the lymphoid tissue inducer (LTi-like cell, a type of innate lymphoid cell. These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling. LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium. Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota. LTi-like cells require IL-1R1 for production of protective cytokines and confer protection in infectious colitis, and their cell numbers in the colon depend upon having a microbiome.

  4. Rearrangements of chicken immunoglobulin genes in lymphoid cells transformed by the avian retroviral oncogene v-rel.

    Science.gov (United States)

    Chen, L; Lim, M Y; Bose, H; Bishop, J M

    1988-01-01

    The retroviral oncogene v-rel transforms poorly characterized lymphoid cells. We have explored the nature of these cells by analyzing the configuration and expression of immunoglobulin genes in chicken hemopoietic cells transformed by v-rel. None of the transformed cells expressed their immunoglobulin genes. The cells fell into three classes: class I cells have their immunoglobulin genes potentially in an embryonic configuration; class II and class III cells have lost one copy of the lambda light chain locus and have one copy of the heavy chain locus rearranged into a configuration that differs from what is found in mature B cells. In class II cells, the other heavy chain locus may be in embryonic configuration, whereas it is deleted in class III cells. The first of these classes may represent the earliest stage of the lymphoid lineage yet encountered among virus-transformed cells, whereas the second and third classes represent an apparently anomalous rearrangement whose origin remains unknown.

  5. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Directory of Open Access Journals (Sweden)

    Misae Tsunaka

    2016-07-01

    Full Text Available Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma, Molt4 (acute T-lymphoblastic leukemia, and Ramos (Burkitt lymphoma were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

  6. Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells.

    LENUS (Irish Health Repository)

    McMenamin, Moya

    2012-09-01

    The aim of this study was to compare the efficacy of endometrial aspiration biopsy (EAB) with the more traditional dilatation and curettage (D&C) for the procurement of lymphoid progenitor cells and uterine natural killer (NK) populations in endometrial tissue. This prospective observational study conducted in a tertiary referral university hospital examined endometrium obtained from 32 women admitted for laparoscopic gynaecological procedures. Each participant had endometrium sampled using both EAB and D&C. Both methods were assessed as a source of uterine NK and lymphoid progenitor cells. Similar proportions of mature CD45+CD56+ NK cells (range 25.4-36.2%) and CD45+CD34+ lymphoid progenitors (range 1.2-2.0%) were found in tissue obtained using both EAB and D&C. These cells were adequate for flow cytometric analysis, magnetic bead separation and culture. Colony formation by the CD34+ population demonstrated maturational potential. Tissues obtained via endometrial biopsy and D&C are equivalent, by analysis of uterine NK and lymphoid progenitor cells. The aim of this study was to compare two methods of endometrial sampling - endometrial aspiration biopsy and traditional dilatation and curettage - for the procurement of haematopoietic stem cells and uterine natural killer (NK) populations in endometrial tissue. Thirty-two women who had gynaecological procedures in a tertiary referral hospital participated in this study and had endometrial tissue collected via both methods. Similar populations of mature NK cells and haematopoietic stem cells were found in tissue obtained using both endometrial aspiration biopsy and dilatation and curettage. Tissue obtained via endometrial aspiration biopsy was adequate for the culture and growth of haematopoietic stem cells. We conclude that tissue obtained via endometrial biopsy and dilatation and curettage is equivalent, by analysis of uterine NK and haematopoietic stem cells using flow cytometry. This has implications for further

  7. Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts

    Energy Technology Data Exchange (ETDEWEB)

    Slavin, S.; Reitz, B.; Bieber, C.P.; Kaplan, H.S.; Strober, S.

    1978-03-01

    Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.

  8. Influence of Resident Intestinal Microflora on the Development and Functions of the Gut-Associated Lymphoid Tissue

    OpenAIRE

    MOREAU, Marie-Christiane; Gaboriau-Routhiau, Valérie

    2011-01-01

    Gut-associated lymphoid tissue (GALT) is under constant exposure to environmental antigens. The digestive flora is the main antigenic stimulus. A huge population of live bacterial cells, estimated at 1014 in number, colonizes the human gastrointestinal tract (1). Bacterial numbers and composition vary considerably along the gastrointestinal tract, constituting complex ecosystems which depend on the physiology of the host and on interactions between bacteria. It has recently been shown that GA...

  9. Viral Interactions in Human Lymphoid Tissue: Human Herpesvirus 7 Suppresses the Replication of CCR5-Tropic Human Immunodeficiency Virus Type 1 via CD4 Modulation▿

    OpenAIRE

    2006-01-01

    Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens that affect the clinical course of HIV disease. Here, we identified another virus, human herpesvirus 7 (HHV-7) that interferes with HIV type 1 (HIV-1) replication in human lymphoid tissue, where critical events of HIV disease occur. Like the closely related HHV-6, HHV-7 suppresses the replication of CCR5-tropic (R5) HIV-1 in coinfected blocks of human lymphoid tissue. Unlike HHV-6, which affect...

  10. Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours

    Science.gov (United States)

    Reiman, A; Srinivasan, V; Barone, G; Last, J I; Wootton, L L; Davies, E G; Verhagen, M M; Willemsen, M A; Weemaes, C M; Byrd, P J; Izatt, L; Easton, D F; Thompson, D J; Taylor, A M

    2011-01-01

    Background: Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T. Methods: From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity. Results: In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype. Conclusion: Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age. PMID:21792198

  11. Dietary intakes and risk of lymphoid and myeloid leukemia in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Science.gov (United States)

    Saberi Hosnijeh, Fatemeh; Peeters, Petra; Romieu, Isabelle; Kelly, Rachel; Riboli, Elio; Olsen, Anja; Tjønneland, Anne; Fagherazzi, Guy; Clavel-Chapelon, Françoise; Dossus, Laure; Nieters, Alexandra; Teucher, Birgit; Trichopoulou, Antonia; Naska, Androniki; Valanou, Elisavet; Mattiello, Amalia; Sieri, Sabina; Parr, Christine L; Engeset, Dagrun; Skeie, Guri; Dorronsoro, Miren; Barricarte, Aurelio; Sánchez, Maria-José; Ericson, Ulrika; Sonestedt, Emily; Bueno-de-Mesquita, H Bas; Ros, Martine M; Travis, Ruth C; Key, Timothy J; Vineis, Paolo; Vermeulen, Roel

    2014-01-01

    The etiology of leukemias cannot entirely be explained by known risk factors, including ionizing radiation, benzene exposure, and infection with human T cell leukemia virus. A number of studies suggested that diet influences the risk of adult leukemias. However, results have been largely inconsistent. We examined the potential association between dietary factors and risk of leukemias among participants of the European Prospective Investigation into Cancer and Nutrition study. Among the 477,325 participants with mean follow-up of 11.34 yr (SD = 2.47), 773 leukemias (373 and 342 cases of lymphoid and myeloid leukemia, respectively) were identified. Diet over the previous 12 mo was assessed at baseline using a validated country-specific dietary questionnaire. Cox proportional hazards regression was used to explore the association between dietary factors that have previously been associated with leukemia risk, including red and processed meat, poultry, offal, fish, dairy products, vegetables, fruits, and seeds/nuts, and risk of both lymphoid and myeloid leukemias. No significant associations were observed between dietary measures and total, lymphoid, and myeloid leukemias. Additional subtype analyses showed no dietary association with risk of major subtypes of leukemias. In summary, this study did not support a possible link between selected dietary factors and risk of leukemias.

  12. Epigenetic Regulation of Non-Lymphoid Cells by Bisphenol A, a Model Endocrine Disrupter: Potential Implications for Immunoregulation.

    Science.gov (United States)

    Khan, Deena; Ahmed, S Ansar

    2015-01-01

    Endocrine disrupting chemicals (EDC) abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical, and consumer product industries. Many of the EDCs such as Bisphenol A (BPA) have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth, and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation, and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight the BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system.

  13. Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station.

    Science.gov (United States)

    Fitzgerald, Wendy; Chen, Silvia; Walz, Carl; Zimmerberg, Joshua; Margolis, Leonid; Grivel, Jean-Charles

    2009-12-01

    The immune responses of human lymphoid tissue explants or cells isolated from this tissue were studied quantitatively under normal gravity and microgravity. Microgravity was either modeled by solid body suspension in a rotating, oxygenated culture vessel or was actually achieved on the International Space Station (ISS). Our experiments demonstrate that tissues or cells challenged by recall antigen or by polyclonal activator in modeled microgravity lose all their ability to produce antibodies and cytokines and to increase their metabolic activity. In contrast, if the cells were challenged before being exposed to modeled microgravity suspension culture, they maintained their responses. Similarly, in microgravity in the ISS, lymphoid cells did not respond to antigenic or polyclonal challenge, whereas cells challenged prior to the space flight maintained their antibody and cytokine responses in space. Thus, immune activation of cells of lymphoid tissue is severely blunted both in modeled and true microgravity. This suggests that suspension culture via solid body rotation is sufficient to induce the changes in cellular physiology seen in true microgravity. This phenomenon may reflect immune dysfunction observed in astronauts during space flights. If so, the ex vivo system described above can be used to understand cellular and molecular mechanisms of this dysfunction.

  14. [Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

    Science.gov (United States)

    Friedrich, T; Ott, G; Kalla, J; Helbig, W; Schwenke, H; Kubel, M; Pönisch, W; Feyer, P; Friedrich, A

    1994-01-01

    In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

  15. PD-L1/PD-1 check-point in gastric carcinoma with lymphoid stroma case report with immunochemical study.

    Science.gov (United States)

    Crescenzi, Anna; Taffon, Chiara; Donati, Michele; Guarino, Michele Pier Luca; Valeri, Sergio; Coppola, Roberto

    2017-02-01

    Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1-programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes. The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery.

  16. Expression of asparagine synthetase predicts in vitro response to L-asparaginase in canine lymphoid cell lines.

    Science.gov (United States)

    Smallwood, Tangi L; Small, George W; Suter, Steven E; Richards, Kristy L

    2014-06-01

    l-asparaginase (L-asp), a bacterial enzyme that depletes extracellular asparagine, is used to treat acute lymphoblastic leukemia in humans and a variety of aggressive lymphoid malignancies in dogs. Resistance to this drug is an important cause of treatment failure in both species. Using canine lymphoid cell lines, we found that L-asp sensitivity is strongly negatively correlated with the level of methylation of the asparagine synthetase (ASNS) promoter. Selection for in vitro resistance was accompanied by increased ASNS promoter methylation and decreased ASNS mRNA expression. In addition, treatment with the hypomethylating agent 5-azacytidine increased resistance to L-asp. ASNS methylation and expression is not predictive of overall survival or progression-free survival in canine lymphoma patients treated with L-asp. Our data suggest that ASNS is an important factor in mediating the in vitro response of canine lymphoid cells to L-asp; however, resistance mechanisms may be more complex in dogs treated clinically with L-asp, potentially due to concurrent treatments.

  17. Antitumor immunity by a dendritic cell vaccine encoding secondary lymphoid chemokine and tumor lysate on murine prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Lu; Qi Zhang; Chun-Min Liang; Shu-Jie Xia; Cui-Ping Zhong; Da-Wei Wang

    2008-01-01

    Aim: To investigate the antitumor immunity by a dendritic cell (DC) vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods: DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine (SLC) cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC+lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results: We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC+lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phos-phate buffer solution (PBS) counterparts (P<0.01). Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4+, CD8+ T cell and CD11c+ DC within established tumor treated by SLC+lysate-DC vaccine than other DC vaccines (P<0.01). Conclusion: DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4+, CD8+ T cell and DC, which might provide a potential immunotherapy method for prostate cancer.

  18. Attempts on producing lymphoid cell line from Penaeus monodon by induction with SV40-T and 12S EIA oncogenes.

    Science.gov (United States)

    Puthumana, Jayesh; Prabhakaran, Priyaja; Philip, Rosamma; Singh, I S Bright

    2015-12-01

    In an attempt of in vitro transformation, transfection mediated expression of Simian virus-40 (T) antigen (SV40-T) and transduction mediated expression of Adenovirus type 12 early region 1A (12S E1A) oncogene were performed in Penaeus monodon lymphoid cells. pSV3-neo vector encoding SV40-T oncogene and a recombinant baculovirus BacP2-12S E1A-GFP encoding 12S E1A oncogene under the control of hybrid promoters were used. Electroporation and lipofection mediated transformation of SV40-T in lymphoid cells confirmed the transgene expression by phenotypic variation and the expression of GFP in co-transfection experiment. The cells transfected by lipofection (≥ 5%) survived for 14 days with lower toxicity (30%), whilst on electroporation, most of the cells succumbed to death (60%) and survived cells lived up to 7 days. Transduction efficiency in primary lymphoid cells was more than 80% within 14 days of post-transduction, however, an incubation period of 7 days post-transduction was observed without detectable expression of 12S E1A. High level of oncogenic 12S E1A expression were observed after 14 day post-transduction and the proliferating cells survived for more than 90 days with GFP expression, however, without in vitro transformation and immortalization. The study put forth the requirement of transduction mediated 'specific' oncogene expression along with telomerase activation and epigenetic induction for the immortalization and establishment of shrimp cell line.

  19. Epigenetic regulation of non-lymphoid cells by Bisphenol-A, a model endocrine disrupter: Potential Implications for Immunoregulation

    Directory of Open Access Journals (Sweden)

    Deena eKhan

    2015-06-01

    Full Text Available Endocrine disrupting chemicals (EDC abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical and consumer product industries. Many of the EDCs such as Bisphenol A (BPA have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system.

  20. Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE.

    Science.gov (United States)

    Hatfield, Julianne K; Brown, Melissa A

    2015-10-01

    Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival. We show that disease-induced trafficking of transferred wild type T cells to the meninges is impaired in ILC3-deficient Rorc-/- mice. Furthermore, lymphoid tissue inducer cells, a c-kit+ ILC3 subset that promotes ectopic lymphoid follicle development, a hallmark of many autoimmune diseases, are reduced in the meninges of EAE-resistant c-kit mutant Kit(W/Wv) mice. We propose that ILC3s sustain neuroinflammation by supporting T cell survival and reactivation in the meninges.