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Sample records for lymphoid tissues confounds

  1. 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),

  2. Confounding

    OpenAIRE

    Andrade, Chittaranjan

    2007-01-01

    Background: Confounding is a statistical concept that is important to all researchers. Materials and Methods: The concept of confounding is explained with the help of an amusing but true example. Simple explanations about and examples of confounding are provided. Methods to deal with confounding are detailed and their applications and disadvantages are examined. Conclusions: Attention to confounding is necessary at the time of study design as well as during the statistical analysis of data. T...

  3. Confounding

    NARCIS (Netherlands)

    Buitendijk, S.E.; Miranda, E. de

    2001-01-01

    Bij observationeel onderzoek is het vaak lastig om te weten van welke risicofactor een geconstateerd effect afkomstig is. Vermenging van effect van verschillende risicofactoren is daarvan vaak de oorzaak. Confounding betekent letterlijk verwarring of verstoring. Het vergelijken van een risico­ f

  4. 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.

  5. 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.

  6. [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.

  7. 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.

  8. Developing hazelnut tissue culture medium free of ion confounding

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    The general approach for tissue culture medium optimization is to use salts as factors in experimental design and analysis. However, using salts as factors leads to ion confounding, making it difficult to detect the effects of individual ions on particular growth responses. This study focused on tes...

  9. 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

  10. 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...

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

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    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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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.

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

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    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

  20. 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.

  1. 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

  2. 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.

  3. 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...

  4. 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...

  5. 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...

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

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    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.

  7. 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

  8. Scrapie-specific pathology of sheep lymphoid tissues.

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    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.

  9. 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

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

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    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. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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).

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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 ...

  5. 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...

  6. 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

  7. 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

  8. 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

  9. 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.

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

    Science.gov (United States)

    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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  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. 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.

  19. 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.

  20. 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

  1. 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.

  2. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage.

    Science.gov (United States)

    Aparicio-Domingo, Patricia; Romera-Hernandez, Monica; Karrich, Julien J; Cornelissen, Ferry; Papazian, Natalie; Lindenbergh-Kortleve, Dicky J; Butler, James A; Boon, Louis; Coles, Mark C; Samsom, Janneke N; Cupedo, Tom

    2015-10-19

    Disruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence of this high mitotic activity, mucosal surfaces are frequently targeted by anticancer therapies, leading to dose-limiting side effects. The cellular mechanisms that control tissue protection and mucosal healing in response to intestinal damage remain poorly understood. Type 3 innate lymphoid cells (ILC3s) are regulators of homeostasis and tissue responses to infection at mucosal surfaces. We now demonstrate that ILC3s are required for epithelial activation and proliferation in response to small intestinal tissue damage induced by the chemotherapeutic agent methotrexate. Multiple subsets of ILC3s are activated after intestinal tissue damage, and in the absence of ILC3s, epithelial activation is lost, correlating with increased pathology and severe damage to the intestinal crypts. Using ILC3-deficient Lgr5 reporter mice, we show that maintenance of intestinal stem cells after damage is severely impaired in the absence of ILC3s or the ILC3 signature cytokine IL-22. These data unveil a novel function of ILC3s in limiting tissue damage by preserving tissue-specific stem cells.

  3. 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.

  4. 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

  5. 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.

  6. [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.

  7. 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.

  8. 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.

  9. [Effects of prebiotics and probiotics on gastrointestinal tract lymphoid tissue in hiv infected patients].

    Science.gov (United States)

    Feria, Manuel G; Taborda, Natalia A; Hernandez, Juan C; Rugeles, María T

    2017-02-01

    HIV infection induces alterations in almost all immune cell populations, mainly in CD4+ T cells, leading to the development of opportunistic infections. The gut-associated lymphoid tissue (GALT) constitutes the most important site for viral replication, because the main target cells, memory T-cells, reside in this tissue. It is currently known that alterations in GALT are critical during the course of the infection, as HIV-1 induces loss of tissue integrity and promotes translocation of microbial products from the intestinal lumen to the systemic circulation, leading to a persistent immune activation state and immune exhaustion. Although antiretroviral treatment decreases viral load and substantially improves the prognosis of the infection, the alterations in GALT remains, having a great impact on the ability to establish effective immune responses. This emphasizes the importance of developing new therapeutic alternatives that may promote structural and functional integrity of this tissue. In this regard, therapy with probiotics/prebiotics has beneficial effects in GALT, mainly in syndromes characterized by intestinal dysbiosis, including the HIV-1 infection. In these patients, the consumption of probiotics/prebiotics decreased microbial products in plasma and CD4+ T cell activation, increased CD4+ T cell frequency, in particular Th17, and improved the intestinal flora. In this review, the most important findings on the potential impact of the probiotics/prebiotics therapy are discussed.

  10. 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

  11. 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.

  12. 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.

  13. Association of Serum CXCL13 with Intrarenal Ectopic Lymphoid Tissue Formation in Lupus Nephritis

    Science.gov (United States)

    Chen, Wen Li; Long, Kang Xia; Zhang, Xiao

    2016-01-01

    Aims. To assess the concentrations of serum CXCL13 and intrarenal ectopic lymphoid tissue (ELT) profiles and their correlation in the patients with lupus nephritis (LN). Methods. Serum CXCL13 levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of CD3, CD20, and CD21 in renal biopsy specimens was tested using immunohistochemical methods. Results. Serum CXCL13 levels were significantly higher in the LN group than those in the SLE group without LN and also in the type III and IV LN patients than in type V LN patients. LN patients with positive CD20 expression (CD20+ LN) had a longer disease course and poorer response to combination therapy and higher serum CXCL13 levels than CD20− LN patients. Moreover, the serum CXCL13 level was positively correlated with the number of B cells/HP in the renal tissue of LN patients. The coexpression patterns of CD3, CD20, and CD21 in the renal tissue of LN patients with different WHO pathological types were significantly different. Serum CXCL13 levels were significantly higher in ELT-2 type LN patients than in 0 or 1 type LN patients. Conclusions. This study suggested that increased serum levels of CXCL13 might be involved in renal ELT formation and renal impairment process in LN. PMID:27990444

  14. Association of Serum CXCL13 with Intrarenal Ectopic Lymphoid Tissue Formation in Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    De Ning He

    2016-01-01

    Full Text Available Aims. To assess the concentrations of serum CXCL13 and intrarenal ectopic lymphoid tissue (ELT profiles and their correlation in the patients with lupus nephritis (LN. Methods. Serum CXCL13 levels were measured using enzyme-linked immunosorbent assays (ELISA. The expression of CD3, CD20, and CD21 in renal biopsy specimens was tested using immunohistochemical methods. Results. Serum CXCL13 levels were significantly higher in the LN group than those in the SLE group without LN and also in the type III and IV LN patients than in type V LN patients. LN patients with positive CD20 expression (CD20+ LN had a longer disease course and poorer response to combination therapy and higher serum CXCL13 levels than CD20− LN patients. Moreover, the serum CXCL13 level was positively correlated with the number of B cells/HP in the renal tissue of LN patients. The coexpression patterns of CD3, CD20, and CD21 in the renal tissue of LN patients with different WHO pathological types were significantly different. Serum CXCL13 levels were significantly higher in ELT-2 type LN patients than in 0 or 1 type LN patients. Conclusions. This study suggested that increased serum levels of CXCL13 might be involved in renal ELT formation and renal impairment process in LN.

  15. 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.

  16. Roles of GlcNAc-6-O-sulfotransferases in lymphoid and nonlymphoid tissues.

    Science.gov (United States)

    Kawashima, Hiroto

    2010-01-01

    Recent studies using sulfotransferase-deficient mice have revealed various physiological functions of sulfated glycans. Studies using gene-targeted mice deficient in both N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2 showed that these sulfotransferases play critical roles in lymphocyte homing. Recent studies indicated that GlcNAc6ST-2 is expressed not only in lymph node high endothelial venules but also in the colonic epithelial cells in mice, and that this sulfotransferase plays a critical role in GlcNAc-6-O-sulfation of the colonic-mucins, as revealed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry of the colonic-mucin O-glycans from wild-type (WT) and GlcNAc6ST-2-deficient mice. After induction of colitis by dextran sulfate sodium, significantly more leukocyte infiltration was observed in the colon of GlcNAc6ST-2-deficient mice than in that of WT mice. These studies demonstrate that GlcNAc-6-O-sulfotransferases play important roles not only in lymphoid tissues but also in nonlymphoid tissues. This chapter describes experimental procedures for assessing the functions of GlcNAc-6-O-sulfotransferases using gene-targeted mice.

  17. Expression of thyroglobulin on follicular dendritic cells of thyroid mucosa-associated lymphoid tissue (MALT lymphoma

    Directory of Open Access Journals (Sweden)

    Munemasa,Mitsuru

    2009-04-01

    Full Text Available

    Reportedly, thyroid mucosa-associated lymphoid tissue (MALT lymphoma is closely associated with Hashimoto's thyroiditis. However, it remains unknown which antigen is closely associated with thyroid MALT lymphoma. We examined whether B cell response to thyroglobulin (Tg, which is a common thyroid-specific autoantigen, is related etiologically to the pathogenesis of thyroid MALT lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD 35 was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT lymphoma, human Tg was detected immunohistochemically in the follicular epithelial cells and follicular dendritic cells (FDCs. These FDCs were positive by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab and for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs, as revealed by the staining pattern of the germinal center;this fact was confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti-CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an autoantigen that is recognized by thyroid MALT lymphoma cells.

  18. IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.

    Science.gov (United States)

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

    2015-03-01

    Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway.

  19. 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;

  20. 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.

  1. 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'.

  2. 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.

  3. Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome

    Institute of Scientific and Technical Information of China (English)

    Milena Todorovic; Miodrag Krstic; Bela Balint; Miodrag Jevtic; Nada Suvajdzic; Amela Ceric; Dragana Stamatovic; Olivera Markovic; Maja Perunicic; Slobodan Marjanovic

    2008-01-01

    AIM: To determine clinical characteristics and treatmentoutcome of gastric lymphoma after chemotherapy and immuno-chemotherapy.METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages I to IV) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H py/or/status assessment (histology and serology).After anti-/-/py/or/treatment and initial chemotherapy,patients were re-examined every 4 mo.RESULTS: Histological regression of the lymphoma wascomplete in 22/34 (64.7%) and partial in 9 (26.5%)patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H py/or/positive patients, the eradication rate was 100%.CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival.

  4. Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.

    Directory of Open Access Journals (Sweden)

    Chee Han Lim

    2014-07-01

    Full Text Available Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.

  5. Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.

    Science.gov (United States)

    Lim, Chee Han; Voedisch, Sabrina; Wahl, Benjamin; Rouf, Syed Fazle; Geffers, Robert; Rhen, Mikael; Pabst, Oliver

    2014-07-01

    Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.

  6. The neurotrophic receptor Ntrk2 directs lymphoid tissue neovascularization during Leishmania donovani infection.

    Directory of Open Access Journals (Sweden)

    Jane E Dalton

    2015-02-01

    Full Text Available The neurotrophic tyrosine kinase receptor type 2 (Ntrk2, also known as TrkB and its ligands brain derived neurotrophic factor (Bdnf, neurotrophin-4 (NT-4/5, and neurotrophin-3 (NT-3 are known primarily for their multiple effects on neuronal differentiation and survival. Here, we provide evidence that Ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. We show that in Leishmania donovani-infected mice, Ntrk2 is aberrantly expressed on splenic endothelial cells and that new maturing blood vessels within the white pulp are intimately associated with F4/80(hiCD11b(loCD11c(+ macrophages that express Bdnf and NT-4/5 and have pro-angiogenic potential in vitro. Furthermore, administration of the small molecule Ntrk2 antagonist ANA-12 to infected mice significantly inhibited white pulp neovascularization but had no effect on red pulp vascular remodeling. We believe this to be the first evidence of the Ntrk2/neurotrophin pathway driving pathogen-induced vascular remodeling in lymphoid tissue. These studies highlight the therapeutic potential of modulating this pathway to inhibit pathological angiogenesis.

  7. Mucosa-Associated Lymphoid-Tissue Lymphoma of the Cecum and Rectum: A Case Report

    Science.gov (United States)

    Nam, Myung Jin; Park, Sung Chan; Hong, Chang Won; Han, Kyung Su; Sohn, Dae Kyung; Park, Weon Seo; Chang, Hee Jin; Oh, Jae Hwan

    2017-01-01

    A colonic mucosa-associated lymphoid-tissue (MALT) lymphoma is relatively rare compared to lymphomas of the stomach or small intestine. We present a case of a MALT lymphoma in the cecum and rectum found during screening colonoscopy. A 54-year-old female, who had undergone right-breast-conserving surgery with axillary dissection due to an invasive ductal carcinoma and a left-breast excisional biopsy due to microcalcification following adjuvant chemoradiation therapy 3 years earlier, was found to have 3-mm-sized smooth elevated lesions in both the cecum and rectum. No pathologic lesion or lymphadenopathy was found at any other site, but chronic gastritis negative for Helicobacter pylori infection was found. The polyps were removed by using an endoscopic biopsy and revealed an extra nodal marginal zone B-cell MALT lymphoma, showing positive for CD3 and CD20 by immunohistochemical staining. The patient underwent close observation without any additional treatment and has shown no evidence of recurrence as of her last visit. PMID:28289662

  8. Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase region.

    Science.gov (United States)

    Yu, Jong W; Jeffrey, Philip D; Ha, Jun Yong; Yang, Xiaolu; Shi, Yigong

    2011-12-27

    The mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase, a key component of the Carma1/Bcl10/MALT1 signalosome, is critical for NF-κB signaling in multiple contexts. MALT1 is thought to function as a scaffold and protease to promote signaling; however, the biochemical and structural basis of paracaspase action remains largely unknown. Here we report the 1.75-Å resolution crystal structure of the MALT1 paracaspase region, which contains the paracaspase domain and an ensuing Ig-like domain. The paracaspase and the Ig domains appear as a single folding unit and interact with each other through extensive van der Waals contacts and hydrogen bonds. The paracaspase domain adopts a fold that is nearly identical to that of classic caspases and homodimerizes similarly to form an active protease. Unlike caspases, the active and mature form of the paracaspase domain remains a single uncleaved polypeptide and specifically recognizes the bound peptide inhibitor Val-Arg-Pro-Arg. In particular, the carboxyl-terminal amino acid Arg of the inhibitor is coordinated by three highly conserved acidic residues. This structure serves as an important framework for deciphering the function and mechanism of paracaspases exemplified by MALT1.

  9. THE IMMUNOHISTOCHEMISTRY AND QUANTITATIVE MORPHOMETRIC STUDY OF MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA IN STOMACH

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To invetigate the Immunohistochemistry characters and quantitative nmorphometric significance for the mucosa associated lymphoid tissue (MALT) lymphoma of stomach in 14 patients. Methods: The routine paraffin slides were cut, stained with H.E., and immunochemically by ABC method. The morphologic appearance of nuclei of lymphoma cells were measured with HPIAS-1000 color pathology picture analysis system. Results of the 14 cases, 9 was centrocyte like (CCL) cell lymphoma, 2 CCL with large cell lymphoma, 1 small no cleaved cell lymphoma, 1 large no cleaved cell lymphoma, 1 T immunoblastic malignant lymphoma. The morphologic measurement results showed that there were great significant differences (P<0.001) for the 15 items of morphology parameters between the nuclei of MALT lymphoma cells and those of normal control lymphocytes in stomach. There were great significance differences (P<0.001) or significance (P<0.05) for the most of the 15 items of morphologic parameters of nuclei among the 5 types of MALT lymphoma. Especially, that the values of area, circumference, equivalent diameter, area volume, circumference volume, long diameter, short diameter, practical area were increasing as the malignant degree of classification was rising, which reflect the increasing malignancy of the tumor. Conclusion: It was suggested that with the quantitative morphology measurement method, man could make accurate diagnosis for MALT lymphoma. It offered us a new method to make the diagnosis, so that it had significance. It might be also practicable with morphology measurement method to make the sub classification of MALT lymphoma.

  10. Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells.

    Science.gov (United States)

    Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M; Franklin, Ruth A; Luo, Chong T; Oh, Soyoung A; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S; Li, Ming O

    2016-01-28

    Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)αβ, and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a, and CD103, these cells share a gene-expression signature distinct from those of conventional NK cells, T cells, and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15 deficiency, but not Nfil3 deficiency, results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type-1-like innate lymphoid cells and type 1 innate-like T cells.

  11. Mucosa-associated lymphoid tissue lymphoma of the transverse colon: A case report

    Institute of Scientific and Technical Information of China (English)

    Shigetoshi Matsuo; Yohei Mizuta; Tomayoshi Hayashi; Seiya Susumu; Ryuji Tsutsumi; Takashi Azuma; Satoshi Yamaguchi

    2006-01-01

    We herein present a case of a 75-year-old female with mucosa-associated lymphoid tissue (MALT) lymphoma of the transverse colon with the stage IE (Ann Arbor classification). Colonoscopy revealed the tumor's appearance as a Ⅱa plus Ⅱc-like early colon cancer as defined ac cording to the macroscopic classification of the Japanese Research Society for Cancer of Colon, Rectum and Anus, measuring less than 2 cm in diameter. Histologically, the tumor was diagnosed as MALT lymphoma because of the presence of lymphoepithelial lesions consisting of diffuse proliferation of atypical lymphocytes and glandular destruction. The majority of these lymphocytes immunohistochemically stained for the B-lymphocyte marker. The patient first utderwent H pylori eradication therapy with Lansap(R). However, the tumor size gradually increased over the next 4 mo and the patient eventually underwent surgical resection. The operative procedure included a partial colectomy with dissection of the paracolic lymph nodes. The tumor measured 45 mm × 30 mm in diam eter and histological examination showed that the lymphoma cells had infiltrated the muscle layer of the colon without nodal involvement. The patient has had no recurrence postoperatively without any chemotherapy.

  12. Development of T Lymphocytes in the Nasal-associated Lymphoid Tissue (NALT from Growing Wistar Rats

    Directory of Open Access Journals (Sweden)

    Gustavo A. Sosa

    2004-01-01

    Full Text Available The aim of the present report was to study the development of several T-lymphocyte subsets in the nasal-associated lymphoid tissue (NALT of growing Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A predominance of CD8α+ over CD4+ T cells was found from 7 to 45 days but from 45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most relevant findings by immunohistochemistry are: (1 the predominance of TCRγδ+ and CD8α+ cells at 7 days postpartum over all the other T-cell subpopulations; and (2 that TCRγβ+ outnumbered TCRαβ+ T cells from 7 to 45 days postpartum whereas αβ T cells predominated in 45- and 60-day-old rats. Besides, cytometric studies have shown that the percentages of TCRγ+, CD8+, as well as the population coexpressing both phenotypes (TCRγδ+CD8α+, were significantly higher in rats at 7 days postpartum when compared to 60 day-old rats. In the present study, the finding of a high number of γδ+ and CD8+ T cells early in NALT development may indicate the importance of these subpopulations in the protection of the nasal mucosa in suckling and weaning Wistar rats.

  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. 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

  15. 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.

  16. 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...

  17. Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration

    Science.gov (United States)

    2016-01-01

    Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0–20 years, 21–40 years, 41–60 years, > 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0–20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p archived beyond 2 years are suboptimal for telomere analysis. PMID:27598341

  18. 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...

  19. Gastric mucosa-associated lymphoid tissue lymphomas and Helicobacter pylori infection: A Colombian perspective

    Institute of Scientific and Technical Information of China (English)

    Sally Yepes; Maria Mercedes Torres; Carlos Saavedra; Rafael Andrade

    2012-01-01

    AIM:To assess the significance of chromosome translocation t(11;18)(q21;q21),B-cell lymphoma 10 (BCL-10)protein and Helicobacter pylori (H.pylori) infection in gastric mucosa-associated lymphoid tissue (MALT) lymphoma in Colombia.METHODS:Fifty cases of gastric MALT lymphoma and their respective post-treatment follow-up biopsies were examined to assess the presence of the translocation t(11;18)(q21;q21) as identified by fluorescence in situ hybridization; to detect protein expression patterns of BCL10 using immunohistochemistry; and for evaluation of tumor histology to determine the correlation of these factors and resistance to H.pylori eradication.RESULTS:Infection with H.pylori was confirmed in all cases of gastric MALT lymphoma in association with chronic gastritis.Bacterial eradication led to tumor regression in 66% of cases.The translocation t(11;18)(q21;q21) was not present in any of these cases,nor was there evidence of tumor transformation to diffuse large B-cell lymphoma.Thirty-four percent of the patients showed resistance to tumor regression,and within this group,7 cases,representing 14% of all those analyzed,were considered to be t(11;18)(q21;q21)-positive gastric MALT lymphomas.Protein expression of BCL10 in the nucleus was associated with the presence of translocation and treatment resistance.Cases that were considered unresponsive to therapy were histologically characterized by the presence of homogeneous tumor cells and a lack of plasmacytic differentiation.Responder cases exhibited higher cellular heterogeneity and a greater frequency of plasma cells.CONCLUSION:Both t(11;18)(q21;q21)-positive MALT lymphoma cases and those with nuclear BCL10 expression are considered resistant to H,pylori eradication.It is suggested that chronic antigenic stimulation is not a dominant event in resistant cases.

  20. Treatment Effects and Sequelae of Radiation Therapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hata, Masaharu, E-mail: mhata@syd.odn.ne.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Omura, Motoko; Koike, Izumi [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Tomita, Naoto [Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Iijima, Yasuhito [Department of Ophthalmology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Tayama, Yoshibumi; Odagiri, Kazumasa; Minagawa, Yumiko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Ogino, Ichiro [Department of Radiation Oncology, Yokohama City University Medical Center, Yokohama, Kanagawa (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan)

    2011-12-01

    Purpose: Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. Methods and Materials: Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage I{sub E}A in 29 patients and stage II{sub E}A in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. Results: All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. Conclusions: Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

  1. Prebiotics modulate immune responses in the gut-associated lymphoid tissue of chickens.

    Science.gov (United States)

    Janardhana, Vijaya; Broadway, Mary M; Bruce, Matthew P; Lowenthal, John W; Geier, Mark S; Hughes, Robert J; Bean, Andrew G D

    2009-07-01

    The recent European Union ban on the prophylactic use of in-feed antibiotics has escalated the search for alternatives for use within the poultry industry. When evaluating the efficacy of potential antibiotic alternatives on bird health and productivity, it is important to analyze the competence of the immune cells in the gut-associated lymphoid tissue (GALT), because it is routinely involved in the surveillance of colonizing microbes as well as in interacting with the ingested feed antigens. Therefore, we studied the effect of the prebiotics mannan-oligosaccharide (MOS) and fructo-oligosaccharide (FOS) on the phenotypic and functional competence of immune cells in cecal tonsil (CT), which is a major GALT. Day-old Cobb 500 male broilers were randomized to 4 groups. Control chickens were fed the basal diet only. Chickens in experimental groups received 0.05 g/kg zinc bacitracin or 5 g/kg of either FOS or MOS in addition to basal diet. At the end of 25 d, our comparison of the experimental groups with controls revealed that the addition of prebiotics to diet resulted in a significant reduction in the proportion of B cells and in mitogen responsiveness of lymphocytes in CT. Furthermore, FOS treatment significantly enhanced the IgM and IgG antibody titers in plasma. These findings emphasize the need for the analyses of the gut immune function following treatment with novel feed additives. The knowledge obtained from such analyses may aid in understanding the mechanisms underlying the immune competence of the birds, which needs consideration when selecting and optimizing new feed additives instead of antibiotics for poultry production.

  2. [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.

  3. Variable levels of tissue mosaicism can confound the interpretation of chromosomal microarray results from peripheral blood.

    Science.gov (United States)

    Pal, Chandni V; Eble, Tanya N; Burnside, Rachel D; Bi, Weimin; Patel, Ankita; Franco, Luis M

    2014-01-01

    Chromosomal microarray analysis (CMA) has significantly increased the ability to diagnose medical conditions caused by copy-number variation in the human genome. Given that the regions involved in copy-number abnormalities often encompass multiple genes, it has been common practice in recent years to compare the phenotypes of individuals with specific copy-number alterations identified by CMA, with the goal of identifying the critical regions for particular elements of a disease phenotype. It is rarely mentioned that this practice relies heavily on the assumption that the absence of mosaicism on CMA from a peripheral blood sample (the most common source of DNA in current clinical practice) reflects the absence of mosaicism in other tissues. We report here a case that violates that assumption. A 28-year-old male with Charcot-Marie-Tooth disease was found by CMA to have a duplication of 17p12 along with two other abnormalities: A duplication of 12p13.33 translocated to the long arm of chromosome 3 and an interstitial duplication of 12p11.23. The patient did not have any clinical features suggestive of 12p duplication syndrome. Chromosomal microarray analysis on skin fibroblasts revealed the duplications at 17p12 and 12p11.23, but not the terminal duplication of 12p13.33. FISH analysis on skin fibroblasts confirmed the presence of very low levels of mosaicism for the terminal 12p duplication. The case illustrates how the absence of mosaicism in blood is not always indicative of the absence of mosaicism in other tissues. Even in an era of high-throughput, highly accurate DNA-based tests, it is important to remember the limitations of testing before drawing conclusions about the relationship between a test results and a clinical phenotype.

  4. 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.

  5. 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.

  6. A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues.

    Science.gov (United States)

    Yu, Yen-Rei A; O'Koren, Emily G; Hotten, Danielle F; Kan, Matthew J; Kopin, David; Nelson, Erik R; Que, Loretta; Gunn, Michael D

    2016-01-01

    Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions.

  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. An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT-type lymphoma

    Directory of Open Access Journals (Sweden)

    Bikram Shrestha

    2016-09-01

    Full Text Available Mucosa-associated lymphoid tissue (MALT-type lymphoma is a relatively rare disease; nevertheless, it is the third most common lymphoma type, accounting for 5–7% of all non-Hodgkin lymphomas. Case series and retrospective analysis published in the literature have suggested that extra gastrointestinal (GI MALT-type lymphoma can occur simultaneously with MALT-type lymphoma involving the GI tract. We report the case of a healthy, 64-year-old Caucasian male who presented with progressive fatigue, non-productive cough, and worsening exertional shortness of breath for 3 months who was subsequently diagnosed with gastric extra-nodal marginal zone B-cell lymphoma or MALToma with simultaneous metastasis to the lung (bronchi based on biopsy reports. Case presentation: A 64-year-old Caucasian male presented to the emergency room complaining of progressive fatigue for 3 months which had progressed to the point of hindering his usual activities of daily living (ADL. He had recently visited his primary care provider for evaluation of a non-productive cough and exertional shortness of breath. A chest radiography obtained at the time showed bilateral infiltrates. He was then treated for atypical pneumonia but his symptoms unfortunately did not improve. Initial investigations in the emergency room revealed severe anemia and a positive stool guaiac test. Imaging showed bilateral pulmonary infiltrates and an irregular gastric mass. Gastric and transbronchial biopsies were suggestive of extra-nodal marginal zone B-cell lymphoma with simultaneous metastasis to the bronchi. He was treated symptomatically with transfusion of packed red blood cells (PRBC and intravenous iron followed by radiotherapy. Helicobacter pylori infection was ruled out eliminating the possibility of treating him with eradication therapy. Conclusion: Although the stomach is the most common and most extensively studied site of involvement of MALT lymphomas, they can also emerge in many other

  9. Quantifying confounding

    NARCIS (Netherlands)

    Groenwold, R.H.H.

    2009-01-01

    In observational studies on causal associations, comparison groups (e.g. groups of treated and untreated subjects) are likely to differ on prognostic characteristics. Such incomparability will bias the association under study, which is referred to as confounding. The studies presented in this thesis

  10. Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of scrapie.

    Science.gov (United States)

    Greenlee, Justin J; Kunkle, Robert A; Richt, Jürgen A; Nicholson, Eric M; Hamir, Amir N

    2014-01-01

    Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted horizontally. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. The purpose of this study was to compare the survival time and PrPSc tissue distribution in sheep with highly resistant and highly susceptible PRNP genotypes after intracranial inoculation of the agent of scrapie. Five sheep each of genotype VRQ/VRQ, VRQ/ARR or ARQ/ARR were inoculated. Sheep were euthanized when clinical signs of scrapie became severe. Clinical signs, microscopic lesions, and western blot profiles were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the 171 polymorphic site with VRQ/VRQ sheep surviving 18 months, whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively. Labeling of PrPSc by immunohistochemistry revealed similar accumulations in central nervous system tissues regardless of host genotype. Immunoreactivity for PrPSc in lymphoid tissue was consistently abundant in VRQ/VRQ, present but confined to tonsil or retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep. The results of this study demonstrate the susceptibility of sheep with the ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in lymphoid tissue.

  11. 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.

  12. Meningeal Tertiary Lymphoid Tissues and Multiple Sclerosis: A Gathering Place for Diverse Types of Immune Cells during CNS Autoimmunity.

    Science.gov (United States)

    Pikor, Natalia B; Prat, Alexandre; Bar-Or, Amit; Gommerman, Jennifer L

    2015-01-01

    Collections of leukocytes in the meningeal space have been documented in Multiple Sclerosis (MS). These meningeal aggregates, which in the context of other autoimmune diseases have often been termed tertiary lymphoid tissues (TLT), have been associated with sub-pial cortical damage and disease progression. However, the key molecular and cellular signals required for their formation and maintenance remain unclear. Herein, we review TLT structures in other disease states in order to provide a framework for understanding these structures in the MS meninges. We then assess the evidence that the meningeal compartment serves as an important nexus for immune cells as well as a location for drainage of antigen into cervical lymph nodes. Extrapolating what is known about the molecular and cellular cues that initiate the formation of leukocyte aggregates in non-lymphoid tissues, we speculate on what signals lead to the formation and maintenance of meningeal TLT structures. Referring to the animal model of MS [experimental autoimmune encephalomyelitis (EAE)], we also explore what is known about these structures in supporting B cell and T cell responses during neuroinflammation. Last, we examine the evidence that connects these structures to ongoing neuropathology. Collectively, our review points to the meningeal compartment as an important player in neuroinflammatory processes. Moreover, we hypothesize that in order to gain insights into pro- and anti-inflammatory properties of lymphocytes in MS, one must understand the cellular scaffolds that support lymphocyte retention within the meninges, thus highlighting the importance of non-immune cells (stromal cells) in the neuroinflammatory process.

  13. Regulatory T cells in HIV-infected immunological nonresponders are increased in blood but depleted in lymphoid tissue and predict immunological reconstitution

    DEFF Research Database (Denmark)

    Gaardbo, Julie C; Hartling, Hans J; Ronit, Andreas;

    2014-01-01

    (CD4 T-cell count 200-500 cells/μL), 30 responders (CD4 T-cell count >500 cells/μL), and 34 healthy controls. Tregs, Treg subpopulations, and intracellular staining for interleukin 10 in peripheral blood were measured using flow cytometry. Foxp3 cells in lymphoid tissue were evaluated using...... immunolabeling. The CD4 T-cell count was determined at inclusion and after 1 year of follow-up. RESULTS: INR displayed high percentage of Tregs and activated Tregs in peripheral blood accompanied by a high percentage of Tregs expressing interleukin 10, whereas numbers of Foxp3 cells in lymphoid tissue were low......BACKGROUND: HIV-infected immunological nonresponders fail to immune reconstitute despite optimal treatment. We hypothesized that regulatory T cells (Tregs) are involved in immunological reconstitution. Tregs and Treg subpopulations were measured in blood and Foxp3 cells in lymphoid tissue...

  14. 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.

  15. Maintenance of anti-Sm/RNP autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory B cells.

    Science.gov (United States)

    Weinstein, Jason S; Delano, Matthew J; Xu, Yuan; Kelly-Scumpia, Kindra M; Nacionales, Dina C; Li, Yi; Lee, Pui Y; Scumpia, Philip O; Yang, Lijun; Sobel, Eric; Moldawer, Lyle L; Reeves, Westley H

    2013-04-15

    Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, it is unclear whether it serves a functional role in autoimmune responses. 2,6,10,14-Tetramethylpentadecane causes chronic peritoneal inflammation and lupus-like disease with autoantibody production and ectopic lymphoid tissue (lipogranuloma) formation. A novel transplantation model was used to show that transplanted lipogranulomas retain their lymphoid structure over a prolonged period in the absence of chronic peritoneal inflammation. Recipients of transplanted lipogranulomas produced anti-U1A autoantibodies derived exclusively from the donor, despite nearly complete repopulation of the transplanted lipogranulomas by host lymphocytes. The presence of ectopic lymphoid tissue alone was insufficient, as an anti-U1A response was not generated by the host in the absence of ongoing peritoneal inflammation. Donor-derived anti-U1A autoantibodies were produced for up to 2 mo by plasma cells/plasmablasts recruited to the ectopic lymphoid tissue by CXCR4. Although CD4(+) T cells were not required for autoantibody production from the transplanted lipogranulomas, de novo generation of anti-U1A plasma cells/plasmablasts was reduced following T cell depletion. Significantly, a population of memory B cells was identified in the bone marrow and spleen that did not produce anti-U1A autoantibodies unless stimulated by LPS to undergo terminal differentiation. We conclude that 2,6,10,14-tetramethylpentadecane promotes the T cell-dependent development of class-switched, autoreactive memory B cells and plasma cells/plasmablasts. The latter home to ectopic lymphoid tissue and continue to produce autoantibodies after transplantation and in the absence of peritoneal inflammation. However, peritoneal inflammation appears necessary to generate autoreactive B cells de novo.

  16. 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.

  17. Mucosa associated lymphoid tissue lymphoma presenting within a solitary anti-mesenteric dilated segment of ileum: a case report

    Directory of Open Access Journals (Sweden)

    Storey Rowland

    2009-01-01

    Full Text Available Abstract Introduction Mucosa associated lymphoid tissue (MALT lymphoma is the third most common non-Hodgkin's lymphoma subtype. Clinical presentation is often insidious as a low-grade lesion and disease tends to remain localised for a long period of time. Ileal involvement is rare and presentation within an area of focal anti-mesenteric ileal wall dilation simulating a large diverticulum has not been reported. Case presentation A 59-year-old man of Caucasian origin presented to a general surgical outpatients clinic with an 18-month history of intermittent upper abdominal pain following meals. Following normal gastroscopy and abdominal ultrasound, a focally dilated segment of ileum was seen on computed tomography and further clarified by barium investigation. Histology of this segment demonstrated MALT lymphoma of the small bowel. Conclusion A solitary focally dilated segment of ileal wall may be neoplastic in nature and surgical resection needs to be considered.

  18. Colonic adenocarcinoma, mucosa associated lymphoid tissue lymphoma and tuberculosis in a segment of colon: A case report

    Institute of Scientific and Technical Information of China (English)

    Ambedkar; Raj; Kulandai; Velu; Banushree; C; Srinivasamurthy; Krishnan; Nagarajan; Ilavarasi; Sinduja

    2014-01-01

    Synchronous occurrence of adenocarcinoma and mucosa associated lymphoid tissue(MALT) lymphoma of colon is rare, and its presence with coexisting tuberculosis is still rarer. To our knowledge, this may be the first case report. In the present report, we describe a 43-year-old female who presented with a history of abdominal pain, fever, loss of weight and loss of appetite. Colonoscopy showed a large ulceroproliferative mass arising from the caecum, biopsy of which showed it to be adenocarcinoma of the colon. A right hemicolectomy was performed and microscopic study of the colon revealed tuberculosis and synchronous adenocarcinoma with lymphoma. Eight of sixteen lymph nodes showed tuberculosis and three of sixteenpericoloniclymphnodes showed metastatic deposits. Immunostains further confirmed the tumour to be adenocarcinoma with MALT lymphoma. We would like to highlight the diagnostic challenges arising from the multi-faceted presentations of these three conditions.

  19. A case of mucosa-associated lymphoid tissue lymphoma forming multiple lymphomatous polyposis in the small intestine

    Institute of Scientific and Technical Information of China (English)

    Naoto Hirata; Shiro Nakamura; Nobuhide Oshitani; Kazuhide Higuchi; Tetsuo Arakawa; Kazunari Tominaga; Kensuke Ohta; Kaori Kadouchi; Hirotoshi Okazaki; Tetsuya Tanigawa; Masatsugu Shiba; Toshio Watanabe; Yasuhiro Fujiwara

    2007-01-01

    A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes. An esophago gastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the duodenum and small intestine, and conventional histological testing revealed non-specific inflammatory changes. Further examinations including the immunohistochemical profiles of the biopsied specimens led us to diagnose the lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, forming multiple lymphomatous polyposis sequentially spreading from duodenal bulb to terminal ileum. According to Lugano's classification, its staging was clinically diagnosed as stage Ⅱ. Two courses of a standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and predonisolone)regimen with rituximab reduced the lesion and the patient had a almost complete response. A 5-year follow-up EGD and histological examinations detected no recurrence of the disease.

  20. Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-12-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE.

  1. Meningeal Tertiary Lymphoid Tissues and Multiple Sclerosis: A gathering place for diverse types of Immune Cells during CNS autoimmunity

    Directory of Open Access Journals (Sweden)

    Natalia ePikor

    2016-01-01

    Full Text Available Collections of leukocytes in the meningeal space have been documented in Multiple Sclerosis (MS. These meningeal aggregates, which in the context of other autoimmune diseases have often been termed Tertiary Lymphoid Tissues (TLT, have been associated with sub-pial cortical damage and disease progression. However, the key molecular and cellular signals required for their formation and maintenance, remain unclear. Herein we review TLT structures in other disease states in order to provide a framework for understanding these structures in the MS meninges. We then assess the evidence that the meningeal compartment serves as an important nexus for immune cells as well as a location for drainage of antigen into the cervical lymph node compartment. Extrapolating what is known about the molecular and cellular cues that initiate the formation of leukocyte aggregates in non-lymphoid tissues, we speculate on what signals lead to the formation and maintenance of meningeal TLT structures. Referring to the animal model of MS (Experimental Autoimmune Encephalomyelitis - EAE, we also explore what is known about these structures in supporting B cell and T cell responses during neuroinflammation. Lastly, we examine the evidence that connects these structures to ongoing neuropathology. Collectively, our review points to the meningeal compartment as an important player in neuroinflammatory processes. Moreover, we hypothesize that in order to gain insights into pro- and anti-inflammatory properties of lymphocytes in MS, one must understand the cellular scaffolds that support lymphocyte retention within the meninges, thus highlighting the importance of non-immune cells (stromal cells in the neuroinflammatory process.

  2. Early biodistribution and persistence of a protective live attenuated SIV vaccine elicits localised innate responses in multiple lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Deborah Ferguson

    Full Text Available Vaccination of Mauritian cynomolgus macaques with the attenuated nef-truncated C8 variant of SIVmac251/32H (SIVmacC8 induces early, potent protection against pathogenic, heterologous challenge before the maturation of cognate immunity. To identify processes that contribute to early protection in this model the pathogenesis, anatomical distribution and viral vaccine kinetics were determined in relation to localised innate responses triggered by vaccination. The early biodistribution of SIVmacC8 was defined by rapid, widespread dissemination amongst multiple lymphoid tissues, detectable after 3 days. Cell-associated viral RNA dynamics identified mesenteric lymph nodes (MLN and spleen, as well as the gut mucosae, as early major contributors of systemic virus burden. Rapid, localised infection was populated by discrete foci of persisting virus-infected cells. Localised productive infection triggered a broad innate response, with type-1 interferon sensitive IRF-7, STAT-1, TRIM5α and ApoBEC3G genes all upregulated during the acute phase but induction did not prevent viral persistence. Profound changes in vaccine-induced cell-surface markers of immune activation were detected on macrophages, B-cells and dendritic cells (DC-SIGN, S-100, CD40, CD11c, CD123 and CD86. Notably, high DC-SIGN and S100 staining for follicular and interdigitating DCs respectively, in MLN and spleen were detected by 3 days, persisting 20 weeks post-vaccination. Although not formally evaluated, the early biodistribution of SIVmacC8 simultaneously targets multiple lymphoid tissues to induce strong innate immune responses coincident at the same sites critical for early protection from wild-type viruses. HIV vaccines which stimulate appropriate innate, as well as adaptive responses, akin to those generated by live attenuated SIV vaccines, may prove the most efficacious.

  3. Bronchus-associated lymphoid tissue (BALT) lymphoma of the lung showing mosaic pattern of inhomogeneous attenuation on thin-section CT: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Jae; Kim, Sung Hwan; Koo, Soo Hyun; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Jang, Kee Taek; Kim, Duck Hwan [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2000-09-01

    The authors present a case of histologically proven bronchus-associated lymphoid tissue (BALT) lymphoma of the lung in a patient with primary Sjogren's syndrome that manifested on thin-section CT scan as a mosaic pattern of inhomogeneous attenuation due to mixed small airway and infiltrative abnormalities.

  4. Retention of Ag-specific memory CD4(+) T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

    Science.gov (United States)

    Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

    2017-03-15

    Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4(+) T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4(+) T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4(+) T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4(+) T-cell populations are generated in peripheral lymph nodes following immunisation.

  5. CD4 and MHC class I down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates

    Science.gov (United States)

    Gray, Lachlan R.; Gabuzda, Dana; Cowley, Daniel; Ellett, Anne; Chiavaroli, Lisa; Wesselingh, Steven L.; Churchill, Melissa J.; Gorry, Paul R.

    2015-01-01

    HIV-1 nef undergoes adaptive evolution in the CNS, reflecting altered requirements for HIV-1 replication in macrophages/microglia and brain-specific immune selection pressures. The role of Nef in HIV-1 neurotropism and the pathogenesis of HIV-associated dementia (HAD) is unclear. In this study, we characterized 82 nef alleles cloned from brain, CSF, spinal cord and blood/lymphoid tissue-derived HIV-1 isolates from 7 subjects with HAD. CNS isolate-derived nef alleles were genetically compartmentalized and had reduced sequence diversity compared to those from lymphoid tissue isolates. Defective nef alleles predominated in a brain-derived isolate from one of the 7 subjects (MACS2-br). The ability of Nef to down-modulate CD4 and MHC class 1 (MHC-1) was generally conserved among nef alleles from both CNS and lymphoid tissues. However, the potency of CD4 and MHC-1 down-modulation was variable, which was associated with sequence alterations known to influence these Nef functions. These results suggest that CD4 and MHC-1 down-modulation are highly conserved functions among nef alleles from CNS- and lymphoid tissue-derived HIV-1 isolates that may contribute to viral replication and escape from immune surveillance in the CNS. PMID:21165790

  6. Primary mucosa-associated lymphoid tissue (MALT) lymphoma of thyroid gland arising from coexisting Hashimoto's thyroiditis: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Kwon; Kwon, Sun Young; Kim, Young Hwan; Choi, Jin Soo; Sohn, Chul Ho; Lee, Hee Jung; Woo, Seong Ku; Suh, Soo Ji [Dongsan Medical Center, Keimyung University, Daegue (Korea, Republic of)

    2006-07-15

    We report herein on a case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland in a 57-year-old woman with coexisting Hashimoto's thyroiditis, and we include its characteristic imaging, histopathologic and immunohistochemical findings.

  7. Gastric marginal zone lymphoma of mucosa-associated lymphoid tissue and signet ring cell carcinoma, synchronous collision tumour of the stomach: a case report.

    Science.gov (United States)

    George, Smiley Annie; Junaid, T A

    2014-01-01

    To report a rare case of synchronous marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) signet ring cell carcinoma occurring as a collision tumour in the stomach. A 53-year-old man was diagnosed initially with signet ring cell carcinoma of the stomach. The microscopy of the subsequent total gastrectomy revealed a collision tumour of MALT lymphoma and signet ring cell carcinoma associated with Helicobacter pylori gastritis. This case highlighted the importance of a careful evaluation of the accompanying lymphoid population in the biopsy samples of gastric adenocarcinoma and underlined the need for multiple endoscopic biopsies to detect these rare synchronous tumours. © 2013 S. Karger AG, Basel.

  8. Immunobiotic Lactobacillus strains augment NLRP3 expression in newborn and adult porcine gut-associated lymphoid tissues.

    Science.gov (United States)

    Tohno, Masanori; Shimosato, Takeshi; Aso, Hisashi; Kitazawa, Haruki

    2011-12-15

    We isolated cDNA encoding porcine nucleotide-binding domain-like receptor family, pryin domain containing 3 (NLRP3) from Peyer's patches. The complete nucleotide open reading frame of porcine NLRP3 contains 3108-bp encoding a deduced polypeptide of 1036-amino acid residues. The porcine NLRP3 amino acid sequence is more similar to the longest isoform of human than the mouse counterpart. The predicted amino acid sequence of porcine NLRP3 presented nine C-terminal leucine-rich repeat domains. In newborn swine, the expression of NLRP3 was detected at higher levels in spleen and mesenteric lymph nodes, while lower levels were observed in intestinal tissues. In adult swine, NLRP3 was strongly expressed in Peyer's patches and the mesenteric lymph nodes, and the expression level in the lower intestinal tissues was comparable to that in spleen. Toll-like receptor and nucleotide-binding domain ligands, as well as Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus gasseri, enhanced NLRP3 expression in gut-associated lymphoid tissues (GALT) of newborn and adult swine. Our results should aid in understanding the intestinal immunoregulatory mechanisms underlying NLRP3 activation and the priming ability of immunobiotic lactic acid bacteria in porcine GALT.

  9. Prevalence of Achromobacter xylosoxidans in pulmonary mucosa-associated lymphoid tissue lymphoma in different regions of Europe.

    Science.gov (United States)

    Adam, Patrick; Czapiewski, Piotr; Colak, Seba; Kosmidis, Perikles; Tousseyn, Thomas; Sagaert, Xavier; Boudova, Ludmila; Okoń, Krzysztof; Morresi-Hauf, Alicia; Agostinelli, Claudio; Pileri, Stefano; Pruneri, Giancarlo; Martinelli, Giovanni; Du, Ming-Qing; Fend, Falko

    2014-03-01

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises 7-8% of B-cell lymphomas and commonly originates from a background of long-standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene-based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram-negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans (P = 0·004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies.

  10. The effect of deoxyribonucleic acid extraction methods from lymphoid tissue on the purity, content, and amplifying ability

    Directory of Open Access Journals (Sweden)

    Hossein Ayatollahi

    2016-01-01

    Full Text Available Background: Nowadays, definitive diagnosis of numerous diseases is based on the genetic and molecular findings. Therefore, preparation of fundamental materials for these evaluations is necessary. Deoxyribonucleic acid (DNA is the first material for the molecular pathology and genetic analysis, and better results need more pure DNA. Furthermore, higher concentration of achieved DNA causes better results and higher amplifying ability for subsequent steps. We aim to evaluate five DNA extraction methods to compare DNA intimacy including purity, concentration, and amplifying ability with each other. Materials and Methods: The lymphoid tissue DNA was extracted from formalin-fixed, paraffin embedded (FFPE tissue through five different methods including phenol-chloroform as the reference method, DNA isolation kit (QIAamp DNA FFPE Tissue Kit, Qiagen, Germany, proteinase K and xylol extraction and heat alkaline plus mineral oil extraction as authorship innovative method. Finally, polymerase chain reaction (PCR and real-time PCR method were assessed to compare each following method consider to DNA purity and its concentration. Results: Among five different applied methods, the highest mean of DNA purity was related to heat alkaline method. Moreover, the highest mean of DNA concentration was related to heat alkaline plus mineral oil. Furthermore, the best result in quantitative PCR was in proteinase K method that had the lowest cycle threshold averages among the other extraction methods. Conclusion: We concluded that our innovative method for DNA extraction (heat alkaline plus mineral oil achieved high DNA purity and concentration.

  11. 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.

  12. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency

    DEFF Research Database (Denmark)

    Simoni, Yannick; Fehlings, Michael; Kloverpris, Henrik N.

    2017-01-01

    to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells...

  13. Clinicopathological Analysis of Pulmonary Marginal Zone B-cell Lymphoma of 
Mucosa-associated Lymphoid Tissue

    Directory of Open Access Journals (Sweden)

    Jing ZENG

    2011-05-01

    Full Text Available Background and objective As a rare disease, pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT, is often misdiagnosed. The aim of this study is to summarize the clinical and pathological features of this disease and improve the awareness of doctors. Methods Seven cases (female 5, male 2 diagnosed of PMZL-MALT in West China Hospital between November 2008 and November 2010, were analyzed retrospectively, including their symptoms, radiological findings, pathological examinations, treatment and prognosis. Results The median age of the patients were 62 years old (range 34-79 years. Six patients suffered from cough and sputum. Pulmonary consolidation was the most frequent manifestation, leading a misdiagnosis of pneumonia with CT examinations. Pathological diagnosis was obtained via fiberoptic bronchoscopy in six patients and percutaneous pulmonary biopsy for the rest one. In the seven cases, immunohistochemical results showed CD20(+, CD79a(+, while CD3 epsilon(-, CD5(-, CyclinD1(-, CD10(-, Bcl-2(- and CD30(-. Additionally, the expression of Ki-67 was below 10%. Further PCR analysis showed evidence of immunoglobulin heavy chain gene rearrangement in tissues from six subjects. Based on the disease location and patients’ wishes, compared with two cases just receiving symptomatic treatments, the other five ones took in chemotherapies. Conclusion Since there were no specific clinical features for patients of PMZL-MALT, histopathological examination was the only effective means to confirm the diagnosis.

  14. 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...

  15. 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

  16. Distinct expression patterns of CD69 in mucosal and systemic lymphoid tissues in primary SIV infection of rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Xiaolei Wang

    Full Text Available Although the intestinal tract plays a major role in early human immunodeficiency virus (HIV infection, the role of immune activation and viral replication in intestinal tissues is not completely understood. Further, increasing evidence suggests the early leukocyte activation antigen CD69 may be involved in the development or regulation of important T cell subsets, as well as a major regulatory molecule of immune responses. Using the simian immunodeficiency virus (SIV rhesus macaque model, we compared expression of CD69 on T cells from the intestine, spleen, lymph nodes, and blood of normal and SIV-infected macaques throughout infection. In uninfected macaques, the majority of intestinal lamina propria CD4+ T cells had a memory (CD95+ phenotype and co-expressed CD69, and essentially all intestinal CCR5+ cells co-expressed CD69. In contrast, systemic lymphoid tissues had far fewer CD69+ T cells, and many had a naïve phenotype. Further, marked, selective depletion of intestinal CD4+CD69+ T cells occurred in early SIV infection, and this depletion persisted throughout infection. Markedly increased levels of CD8+CD69+ T cells were detected after SIV infection in virtually all tissues, including the intestine. Further, confocal microscopy demonstrated selective, productive infection of CD3+CD69+ T cells in the intestine in early infection. Combined, these results indicate CD69+CD4+ T cells are a major early target for viral infection, and their rapid loss by direct infection may have profound effects on intestinal immune regulation in HIV infected patients.

  17. 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.

  18. Distribution of Lymphocytes in the Mucosa Associated Lymphoid Tissues (MALT of Naturally Occurring Infectious Bursal Disease (IBD in Chicken

    Directory of Open Access Journals (Sweden)

    M. M. Uddin*, M. Z. I. Khan1, K. N. Islam, A. S. M. G. Kibria, G. N. Adhikary2, M. N. H. Parvez3, J. Basu, M. B. Uddin4 and M. M. Rahman5

    2010-04-01

    Full Text Available This study was aimed to investigate changes in the number and distribution of lymphocytes in the mucosa associated lymphoid tissues (MALT of digestive tract (proventriculus, duodenum, jejunum, ileum, cecum and cecal tonsils and respiratory system (lungs of chicken infected by Infectious Bursal Disease Virus (IBDV. Samples were divided into two groups; IBDV infected group (21, 24 and 30 days old and control group (non infected birds; 21 days old. Haematoxylin and eosin stained slides were prepared for microscopic studies to observe the distribution and the number of lymphocytes in the mucosa of the digestive tract and respiratory system. Lymphocytes were significantly (P<0.05 lower in proventriculus, duodenum, jejunum, ileum, cecum, cecal tonsils and lungs of IBDV infected chickens than the control. Moreover, the reduction in lymphocytes number was maximum in duodenum and cecal tonsils, while minimal in lungs. Depletion of lymphocyte was mainly in the lamina propria and the core of the villi and depletion increased with the advance of age of IBDV infected chicken. These results demonstrate that IBDV destroys the lymphocytes of the MALT and suppresses the immunity.

  19. Correlation of Endoscopic Findings of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma with Recurrence after Complete Remission

    Science.gov (United States)

    Lee, Chang Min; Lee, Dong Ho; Ahn, Byung Kyu; Hwang, Jae Jin; Yoon, Hyuk; Park, Young Soo; Shin, Cheol Min; Kim, Nayoung

    2017-01-01

    Background/Aims In gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the clinical significance of various endoscopic findings has not yet been determined. This study aimed to compare the time to complete remission (CR) and relapse-free survival (RFS) in gastric MALT lymphoma based on endoscopic findings. Methods In this single-center retrospective cohort study, the medical records of 122 consecutive adult patients with gastric MALT lymphoma were collected over a period of 12 years. CR was defined by the absence of macroscopic or microscopic features of lymphoma on two subsequent follow-ups. Relapse was clinically defined by a positive endoscopic biopsy after CR. Results The median time to CR did not differ significantly between treatment methods. However, it was significantly longer in the group with polypoid endoscopic appearance than in the groups with diffuse infiltration or ulceration (7.83, 3.43, and 3.10 months, respectively; p=0.003). Six patients relapsed after CR. Kaplan-Meier analysis showed that RFS differed significantly between groups based on Ann Arbor staging, treatment methods, and initial endoscopic findings. Conclusions In gastric MALT lymphoma, the endoscopically defined polypoid type was characterized by a longer duration to CR, with a higher likelihood of recurrence, compared to the endoscopically defined diffuse infiltration or ulceration types. PMID:27009028

  20. THE CLINICAL PATHOLOGY AND DNA PLOIDY OF GASTRIC MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA INFILTRATING THE LEIOMYOMAS OF THE UTERUS

    Institute of Scientific and Technical Information of China (English)

    Lü Xiang; LI Xiangzhou; WANG Yihua; DAI Xiaobo

    1999-01-01

    Objective: To investigate the clinicopathology and DNA ploidy of gastric mucosa associated lymphoid tissue (MALT) lymphoma infiltraving the leiomyomas of the uterus of a patient. Methods: The routine paraffin slides were cut, stained with HE, immunochemically by ABC methodusing the and stained by Feulgen method.Then the DNA ploidy of tumor cells was measured with an image cytometer. Results: In the mucosa, submucosa and the smooth muscle layer of the stomach and in the leiomyomas of the uterus there was diffusive and dense infiltration of centrocyte-like cells. The DNA measurement results were that the distribution of DNA mass of lymphoma cells in stomach and in lymph nodes had a single main aneuploidy peak each, and the distribution of DNA mass of lymphoma cells in leiomyomas of uterus had two peaks; one of them was the diploid, the other aneuploid. Conclusion: The MALT lymphoma cell invasion in uterus must be differentiated with a primary lymphoma in the uterus, the chronic lymphocyte leukemia in uterus and an endometrial stromal sarcoma. The present prognosis of the patient under discussion was poor. The follow-up results indicated the DNA index seemed to be important for predicting the malignancy degree and prognosis.

  1. Food allergens and mucosal immune systems with special reference to recognition of food allergens by gut-associated lymphoid tissue

    Directory of Open Access Journals (Sweden)

    Shuichi Kaminogawa

    1999-01-01

    Full Text Available Food allergy, triggered by an aberrant immune response elicited by orally ingested food allergens, is generated through a complicated mechanism because the allergen interacts with the mucosal immune system (the gut- associated lymphoid tissue, GALT and the resulting immune response affects the generation of allergy. This review will describe the process by which antigens or allergens are recognized by the GALT and the characteristic immune responses induced thereafter. Orally administered antigens induce distinct immune responses in the Peyer's patches, lamina propria and the intestinal epithelium. In addition to these local immune responses in the gut, ingested antigens are known to affect systemic immunity. These may induce a suppressed state of systemic immune responsiveness, which is called oral tolerance, or in some cases they may elicit a systemic IgE antibody response which may lead to allergic reactions. Information on the regions on food allergens recognized by T cells and IgE antibodies is important in understanding the fates of food allergens after being recognized by the GALT. The structure of T and B cell epitopes on food allergens and the possibility of modulation of allergic reactions by amino-acid substituted analogs of allergen- derived peptides will also be discussed.

  2. Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue lymphoma

    Institute of Scientific and Technical Information of China (English)

    Hong-Ling Li; Bing-Zhong Sun; Fu-Cheng Ma

    2004-01-01

    AIM:To assess the expression of cyclooxygenase-2 (COX-2),nitric oxide synthase (iNOS), p53 and Ki-67 in gastric mucosaassociated lymphoid tissue (MALT) lymphoma and clarify the relationship between COX-2 expression and iNOS or p53 expression in these patients.METHODS: The expressions of COX-2, iNOS, p53 and Ki-67 were detected in 32 gastric MALT lymphoma specimens and 10 adjacent mucosal specimens by immunohistochemical Envision method.RESULTS: COX-2 and iNOS expressions were significantly higher in gastric MALT lymphoma tissues than those in adjacent normal tissues. The expression of COX-2 was observed in 22 of 32 cases of MALT lymphoma tissues(68.8%). A positive cytoplasmic immunoreactivity for iNOS was detected in 17 of 31 cases (53.1%). COX-2 expression in gastric MALT lymphoma tissues was positively correlated with iNOS expression (r=0.448, P=0.010) and cell proliferative activity analyzed by Ki-67 labeling index (r=0.410, P=0.020).The expression of COX-2 protein did not correlate with age,sex, stage of disease, lymph node metastasis or differentiation.The accumulation of p53 nuclear phosphoprotein was detected in 19(59.4%) of tumors. p53 protein was expressed in 11 of 23 assessed LG tumors and in 8 of 9 assessed HG tumors.The difference of p53 positivity was found statistically significant between LG and HG cases (P=0.0302). The p53 accumulation correlated with advanced clinical stage (stage Ⅲ+Ⅳ vs stage Ⅰ+Ⅱ, P=-0.017). There was a significant positive correlation between COX-2 expression and p53 accumulation status (r=0.403, P=0.022). The mean PI of Ki-67 in each grade group were 36.0±7.73% in HG and 27.4±9.21% in LG. High-proliferation rate correlated with HG tumors (r=0.419, P=0.017). The correlation coefficient showed a significant positive correlation between PI and COX-2 expression in MALT lymphoma patients (r=0.410,P=0.020).CONCLUSION: COX-2 expresses in the majority of gastric MALT lymphoma tissues and correlates with cellular

  3. Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38α-Dependent Restraint of NF-κB Signaling.

    Science.gov (United States)

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2016-03-01

    The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. In this study, we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy.

  4. 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.

  5. Inhibition of TGF-β and EGF pathway gene expression and migration of oral carcinoma cells by mucosa-associated lymphoid tissue 1

    OpenAIRE

    Ohyama, Y.; Kawamoto, Y.; Chiba, T.; Maeda, G.; Sakashita, H; Imai, K.

    2013-01-01

    Background: Expression of mucosa-associated lymphoid tissue 1 (MALT1) is inactivated in oral carcinoma patients with worse prognosis. However, the role in carcinoma progression is unknown. Unveiling genes under the control of MALT1 is necessary to understand the pathology of carcinomas. Methods: Gene data set differentially transcribed in MALT1-stably expressing and -marginally expressing oral carcinoma cells was profiled by the microarray analysis and subjected to the pathway analysis. Migra...

  6. Identification of dendritic cells, B cell and T cell subsets in Tasmanian devil lymphoid tissue; evidence for poor immune cell infiltration into devil facial tumors.

    Science.gov (United States)

    Howson, Lauren J; Morris, Katrina M; Kobayashi, Takumi; Tovar, Cesar; Kreiss, Alexandre; Papenfuss, Anthony T; Corcoran, Lynn; Belov, Katherine; Woods, Gregory M

    2014-05-01

    The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. T and B cell analysis has been limited by a lack of antibodies, hence the need to produce such reagents. Amino acid sequence analysis revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials. Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating bacterial fusion proteins. These, and commercial antibodies against CD1a and CD83, identified T cells, B cells and dendritic cells by immunohistochemistry. CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical distribution was characteristic of mammalian lymphoid tissues with more CD4(+) than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells. Dendritic cells were identified in lymph node, spleen and skin. This distribution is consistent with eutherian mammals and other marsupials, indicating they have the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or IgG(+) B cells, consistent with poor immune cell infiltration.

  7. Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Diana Fleissner

    Full Text Available BACKGROUND: In contrast to intestinal CD4(+ regulatory T cells (T(regs, the generation and function of immunomodulatory intestinal CD8(+ T cells is less well defined. To dissect the immunologic mechanisms of CD8(+ T cell function in the mucosa, reactivity against hemagglutinin (HA expressed in intestinal epithelial cells of mice bearing a MHC class-I-restricted T-cell-receptor specific for HA was studied. METHODOLOGY AND PRINCIPAL FINDINGS: HA-specific CD8(+ T cells were isolated from gut-associated tissues and phenotypically and functionally characterized for the expression of Foxp3(+ and their suppressive capacity. We demonstrate that intestinal HA expression led to peripheral induction of HA-specific CD8(+Foxp3(+ T cells. Antigen-experienced CD8(+ T cells in this transgenic mouse model suppressed the proliferation of CD8(+ and CD4(+ T cells in vitro. Gene expression analysis of suppressive HA-specific CD8(+ T cells revealed a specific up-regulation of CD103, Nrp1, Tnfrsf9 and Pdcd1, molecules also expressed on CD4(+ T(reg subsets. Finally, gut-associated dendritic cells were able to induce HA-specific CD8(+Foxp3(+ T cells. CONCLUSION AND SIGNIFICANCE: We demonstrate that gut specific antigen presentation is sufficient to induce CD8(+ T(regsin vivo which may maintain intestinal homeostasis by down-modulating effector functions of T cells.

  8. Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue.

    Science.gov (United States)

    Doitsh, Gilad; Cavrois, Marielle; Lassen, Kara G; Zepeda, Orlando; Yang, Zhiyuan; Santiago, Mario L; Hebbeler, Andrew M; Greene, Warner C

    2010-11-24

    The mechanism by which CD4 T cells are depleted in HIV-infected hosts remains poorly understood. In ex vivo cultures of human tonsil tissue, CD4 T cells undergo a pronounced cytopathic response following HIV infection. Strikingly, >95% of these dying cells are not productively infected but instead correspond to bystander cells. We now show that the death of these "bystander" cells involves abortive HIV infection. Inhibitors blocking HIV entry or early steps of reverse transcription prevent CD4 T cell death while inhibition of later events in the viral life cycle does not. We demonstrate that the nonpermissive state exhibited by the majority of resting CD4 tonsil T cells leads to accumulation of incomplete reverse transcripts. These cytoplasmic nucleic acids activate a host defense program that elicits a coordinated proapoptotic and proinflammatory response involving caspase-3 and caspase-1 activation. While this response likely evolved to protect the host, it centrally contributes to the immunopathogenic effects of HIV. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Abortive HIV Infection Mediates CD4 T-Cell Depletion and Inflammation in Human Lymphoid Tissue

    Science.gov (United States)

    Doitsh, Gilad; Cavrois, Marielle; Lassen, Kara G.; Zepeda, Orlando; Yang, Zhiyuan; Santiago, Mario L.; Hebbeler, Andrew M.; Greene, Warner C.

    2010-01-01

    Summary The mechanism by which CD4 T-cells are depleted in HIV-infected hosts remains poorly understood. In ex vivo cultures of human tonsil tissue, CD4 T cells undergo a pronounced cytopathic response following HIV infection. Strikingly, >95% of these dying cells are not productively infected but instead correspond to bystander cells. We now show that the death of these “bystander” cells involves abortive HIV infection. Inhibitors blocking HIV entry or early steps of reverse transcription prevent CD4 T-cell death while inhibition of later events in viral life cycle does not. We propose that the nonpermissive state exhibited by the majority of resting CD4 tonsil T-cells leads to accumulation of incomplete reverse transcripts. These cytoplasmic nucleic acids activate a host defense program that elicits a coordinated proapoptotic and proinflammatory response involving caspase-3 and caspase-1 activation. While this response likely evolved to protect the host, it centrally contributes to the immunopathogenic effects of HIV. PMID:21111238

  10. Atypical Epstein-Barr viral genomic structure in lymphoma tissue and lymphoid cell lines.

    Science.gov (United States)

    Tang, Weihua; Fan, Hongxin; Schroeder, Jane; Dunphy, Cherie H; Bryant, Ronald J; Fedoriw, Yuri; Gulley, Margaret L

    2013-06-01

    Epstein-Barr virus (EBV) DNA is found within the malignant cells of some subtypes of lymphoma, and viral presence is being exploited for improved diagnosis, monitoring, and management of affected patients. Recent work suggests that viral genomic polymorphism, such as partial deletion of the viral genome, could interfere with virus detection in tumor tissues. To test for atypical forms of the EBV genome, 98 lymphomas and 6 infected cell lines were studied using a battery of 6 quantitative polymerase chain reaction assays targeting disparate sections of EBV DNA. Fifty of the lymphomas (51%) had no amplifiable EBV DNA, and 38 lymphomas (39%) had low-level EBV infection that was deemed incidental based on EBV-encoded RNA (EBER) in situ hybridization results. The remaining 10 lymphomas (10%) had high EBV loads and EBER localization to malignant cells by EBER in situ hybridization. All 10 represented lymphoma subtypes were previously associated with EBV (Burkitt, diffuse large B-cell, or T-cell type), whereas no remnants of EBV were detected in other lymphoma subtypes (follicular, small lymphocytic, mantle cell, or marginal zone type). Interestingly, 4 of the 10 infected lymphomas had evidence of atypical viral genomes, including 3 of 4 infected T-cell lymphomas with aberrant loss of LMP2 amplicons, and a single diffuse large B-cell lymphoma lacking the central part of the viral genome spanning BamH1W, BZLF1, and EBNA1 gene segments. A reasonable screening strategy for infected malignancy involves applying EBER1 and LMP1 quantitative polymerase chain reaction assays and confirming that values exceeding 2000 copies of EBV per 100,000 cells have EBER localization to malignant cells.

  11. Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6.

    Science.gov (United States)

    Grivel, J C; Ito, Y; Fagà, G; Santoro, F; Shaheen, F; Malnati, M S; Fitzgerald, W; Lusso, P; Margolis, L

    2001-11-01

    HIV-1 infects target cells via a receptor complex formed by CD4 and a chemokine receptor, primarily CCR5 or CXCR4 (ref. 1). Commonly, HIV-1 transmission is mediated by CCR5-tropic variants, also designated slow/low, non-syncytia-inducer or macrophage-tropic, which dominate the early stages of HIV-1 infection and frequently persist during the entire course of the disease. In contrast, HIV-1 variants that use CXCR4 are typically detected at the later stages, and are associated with a rapid decline in CD4+ T cells and progression to AIDS (refs. 2,7-11). Disease progression is also associated with the emergence of concurrent infections that may affect the course of HIV disease by unknown mechanisms. A lymphotropic agent frequently reactivated in HIV-infected patients is human herpesvirus 6 (HHV-6), which has been proposed as a cofactor in AIDS progression. Here we show that in human lymphoid tissue ex vivo, HHV-6 affects HIV-1 infection in a coreceptor-dependent manner, suppressing CCR5-tropic but not CXCR4-tropic HIV-1 replication, as shown with both uncloned viral isolates and isogenic molecular chimeras. Furthermore, we demonstrate that HHV-6 increases the production of the CCR5 ligand RANTES ('regulated upon activation, normal T-cell expressed and secreted'), the most potent HIV-inhibitory CC chemokine, and that exogenous RANTES mimics the effects of HHV-6 on HIV-1, providing a mechanism for the selective blockade of CCR5-tropic HIV-1. Our data suggest that HHV-6 may profoundly influence the course of HIV-1 infection.

  12. Analysis of API2-MALT1 fusion, trisomies, and immunoglobulin VH genes in pulmonary mucosa-associated lymphoid tissue lymphoma.

    Science.gov (United States)

    Xia, Hongjing; Nakayama, Takahisa; Sakuma, Hidenori; Yamada, Seiji; Sato, Fumihiko; Takino, Hisashi; Okabe, Mitsukuni; Fujiyoshi, Yukio; Hattori, Hideo; Inagaki, Hiroshi

    2011-09-01

    Pulmonary mucosa-associated lymphoid tissue lymphoma is unique in that chronic inflammation is rare and that API2-MALT1 fusion, resulting from t(11;18)(q21;q21), occurs frequently. In this study, we examined 20 cases for API2-MALT1 fusion using the multiplex reverse-transcription polymerase chain reaction and looked for trisomy 3, trisomy 18, and abnormalities of MALT1 and IGH genes using fluorescence in situ hybridization. In addition, we analyzed VH genes by subcloning of the monoclonal polymerase chain reaction products. Of 20 cases studied, we detected gene abnormalities in 16: API2-MALT1 fusion in 9, trisomy 3 in 5, trisomy 18 in 4, MALT1 abnormality in 13, and IGH abnormality in 1. MALT1 gene abnormalities were concordant with API2-MALT1 fusion or trisomy 18. One case showed API2-MALT1 fusion and trisomy 3. On detection of API2-MALT1 fusion and trisomies, we were able to divide our cases into 3 groups, API2-MALT1 positive, trisomy positive, and no detectable gene abnormality, suggesting that tumor development had processed along different genetic pathways. All 20 cases were analyzed for VH genes. Most of the VH genes selected by the lymphomas belonged to the VH3 family, but there was no restriction to any particular VH fragment. Of interest, VH genes were unmutated in 7 cases, suggesting that T-cell-independent extrafollicular B-cell maturation may be important in the development of this lymphoma. In addition, both mutated and unmutated tumor cases were found to carry the API2-MALT1 fusion and trisomy 3. This observation suggests that these gene abnormalities may occur in microenvironments found before or outside of follicular germinal centers.

  13. Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: Dose-volumetric analysis and its clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyeon Won; Kim, Tae Hyun; Choi, Il Ju; Kim, Chan Gyoo; Lee, Jong Yeul; Cho, Soo Jeong; Eom, Hyeon Seok; Moon, Sung Ho; Kim, Dae Yong [Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2016-09-15

    To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, Dmax and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and Dmean and V15 for right kidney and Dmean for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys.

  14. Primary endobronchial marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: CT findings 7 patients

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ra Gyoung; Kim, Mi Young; Song, Jae Woo; Chae, Eun Jin; Choi, Chang Min; Jang, Se Jin [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2013-04-15

    To investigate CT and 1{sup 8F}-fluorodeoxyglucose (1{sup 8F}-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT). From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and 1{sup 8F}-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening. A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On 1{sup 8F}-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake. Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on 1{sup 8F}-FDG-PET/CT.

  15. 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.

  16. Hypertrophy, hyperplasia, and infectious virus in gut-associated lymphoid tissue of mice after oral inoculation with simian-human or bovine-human reassortant rotaviruses.

    Science.gov (United States)

    Moser, C A; Dolfi, D V; Di Vietro, M L; Heaton, P A; Offit, P A; Clark, H F

    2001-04-01

    Oral inoculation of infants with a vaccine that contains simian-human reassortant rotaviruses has been found to be a rare cause of intussusception. Because intussusception can be associated with enlargement of gut-associated lymphoid tissue, we studied the capacity of simian-human and bovine-human reassortant rotaviruses to cause lymphoid hypertrophy and hyperplasia of Peyer's patches (PP) of adult BALB/c mice. Neither hypertrophy nor hyperplasia was detected in PP after oral inoculation with simian-human or bovine-human reassortant rotaviruses. However, infectious virus was detected in PP and mesenteric lymph nodes after oral inoculation with simian, but not bovine, reassortant rotaviruses. Implications of these findings on the pathogenesis of intussusception are discussed.

  17. Viral interactions in human lymphoid tissue: Human herpesvirus 7 suppresses the replication of CCR5-tropic human immunodeficiency virus type 1 via CD4 modulation.

    Science.gov (United States)

    Lisco, Andrea; Grivel, Jean-Charles; Biancotto, Angélique; Vanpouille, Christophe; Origgi, Francesco; Malnati, Mauro S; Schols, Dominique; Lusso, Paolo; Margolis, Leonid B

    2007-01-01

    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 affects HIV-1 by upregulating RANTES, HHV-7 did not upregulate any CCR5-binding chemokine. Rather, the inhibition of R5 HIV-1 by HHV-7 was associated with a marked downregulation of CD4, the cellular receptor shared by HHV-7 and HIV-1. HHV-7-induced CD4 downregulation was sufficient for HIV-1 inhibition, since comparable downregulation of CD4 with cyclotriazadisulfonamide, a synthetic macrocycle that specifically modulates expression of CD4, resulted in the suppression of HIV infection similar to that seen in HHV-7-infected tissues. In contrast to R5 HIV-1, CXCR4-tropic (X4) HIV-1 was only minimally suppressed by HHV-7 coinfection. This selectivity in suppression of R5 and X4 HIV-1 is explained by a suppression of HHV-7 replication in X4- but not in R5-coinfected tissues. These results suggest that HIV-1 and HHV-7 may interfere in lymphoid tissue in vivo, thus potentially affecting the progression of HIV-1 disease. Knowledge of the mechanisms of interaction of HIV-1 with HHV-7, as well as with other pathogens that modulate HIV-1 replication, may provide new insights into HIV pathogenesis and lead to the development of new anti-HIV therapeutic strategies.

  18. 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....

  19. A replication analysis of foot-and-mouth disease virus in swine lymphoid tissue might indicate a putative carrier stage in pigs

    Directory of Open Access Journals (Sweden)

    Rodríguez-Calvo Teresa

    2011-02-01

    Full Text Available Abstract Foot-and-mouth disease virus (FMVD, one of the most contagious viruses of cloven-hoofed animals, may cause a prolonged, asymptomatic but persistent infection in ruminants, named the "carrier state". However, it remains an open question whether this carrier state occurs in pigs. Here we present quantitative analyses of the duration of FMDV RNA and infectivity in lymphoid and epithelial tissues in experimentally infected pigs with FMDV C-S8c1. The data indicated that although FMDV RNA remained in blood until day 14 post-infection (pi, viremia was cleared by day 7 pi. However, all tissues tested were positive for FMDV until day 14-17 pi. Interestingly, the specific infectivity of FMDV in these tissues was in some cases even higher than the FMDV C-S8c1. We therefore propose that a "pseudopersistent state" may occur in pigs in which virus replicates in lymphoid tissues for a prolonged period of time, thereby representing a potential source of virus.

  20. Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study

    Energy Technology Data Exchange (ETDEWEB)

    Anacak, Yavuz, E-mail: yavuz.anacak@ege.edu.tr [Department of Radiation Oncology, Ege University Medical School, Izmir (Turkey); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Constantinou, Nikos [Department of Hematology, Theagenion Cancer Center, Thessaloniki (Greece); Mamusa, Angela M. [Division of Hematology, Armando Businco Cancer Center, Cagliari (Italy); Epelbaum, Ron [Department of Oncology, Rambam Medical Center, Haifa (Israel); Li Yexiong [Department of Radiation Oncology, Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Calduch, Anna Lucas [Servicio de Oncologia Radioterapica, Institut Catala d' Oncologia, Barcelona (Spain); Kowalczyk, Anna [Department of Oncology and Radiotherapy, Medical University of Gdansk (Poland); Weber, Damien C. [Department of Radiation Oncology, Geneva University Hospital (Switzerland); Kadish, Sidney P. [Department of Radiation Oncology, University of Massachusetts Medical School/Center, North Worcester, MA (United States); Bese, Nuran [Department of Radiation Oncology, Istanbul University Cerrahpasa Medical School, Istanbul (Turkey); Poortmans, Philip [Institute Verbeeten, Tilburg (Netherlands); Kamer, Serra [Department of Radiation Oncology, Ege University Medical School, Izmir (Turkey); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)

    2012-01-01

    Purpose: Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands. Methods and Materials: Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIE in 12, IIIE in 2, and IV in 15 patients. Results: Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01). Conclusions: To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease-free survival.

  1. 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.

  2. Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

    Science.gov (United States)

    Merchant, Hamid A; McConnell, Emma L; Liu, Fang; Ramaswamy, Chandrasekaran; Kulkarni, Rucha P; Basit, Abdul W; Murdan, Sudaxshina

    2011-01-18

    Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pigpig). The lymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig reiterates the crucial importance of correctly selecting animal models for pre-clinical studies.

  3. Selective chemotaxis of subsets of B lymphocytes from gut-associated lymphoid tissue and its implications for the recruitment of mucosal plasma cells.

    Science.gov (United States)

    Czinn, S J; Lamm, M E

    1986-05-15

    As they differentiate, precursor cells from the gut-associated lymphoid tissue are known to travel via the lymphatic system to the blood and then preferentially to home to various mucosal and exocrine sites such as the lamina propria of the gut and the lactating mammary gland, where they give rise to IgA-secreting plasma cells. The present study, directed at the mechanism by which the circulating precursors of mucosal IgA plasma cells selectively lodge in characteristic locations, explored the hypothesis that such homing is due to a locally produced chemotactic factor and that milk might be a source of such a factor. Subsets of lymphocytes bearing particular surface markers and purified by panning from lymph nodes of mice were examined in a micropore chemotaxis assay to search for the presence of chemotactic activity in mouse milk. The globulin fraction of whey was shown to contain a nondialyzable factor that is chemotactic for IgA (and also IgG)-positive lymphocytes when these are obtained from mesenteric lymph nodes as a source of mucosal-associated lymphoid tissue. Lymphocytes from peripheral lymph nodes, nonmucosal associated, were unaffected as were surface IgM-positive lymphocytes and T lymphocytes obtained from mesenteric nodes. Chemotactic activity for IgA lymphocytes was undetectable in mouse serum. The data are consistent with the idea that precursors of mucosal IgA plasma cells home to mucosal and exocrine sites in response to a specific chemotactic factor elaborated by local differentiated epithelial cells.

  4. Novel region within the V kappa gene promoter is responsible for tissue and stage-specific expression of immunoglobulin genes in human lymphoid neoplasms.

    Science.gov (United States)

    Kossakowska, A E; Urbanski, S J

    1989-03-01

    Immunoglobulin gene-specific transacting factors have been shown to play a role in lymphoid tissue-specific expression of immunoglobulin genes. The role of these factors in B-cell differentiation and stage-specific expression of these genes is, however, not fully understood. We have used a model of human lymphoid neoplasia to address this question. Different fragments of unrearranged human variable region of immunoglobulin kappa gene (V kappa) were used for cell-free in vitro transcription and DNA mobility shift assays. Previously described enhancement of in vitro transcription that was only seen with nuclear extracts derived from B-cell neoplasms corresponding to the late stages of B-cell differentiation was shown to be dependent on the actions of these factor(s) on the DNA region within the V kappa gene promoter. This region is located within the 920 bp fragment located 210 bp upstream from the coding region and this fragment represents a possible novel DNA region, which plays a role in the stage- and tissue-specific expression of immunoglobulin genes.

  5. Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4

    Directory of Open Access Journals (Sweden)

    Maria F. Peralta

    2017-05-01

    Full Text Available Immunoglobulin Y (IgY is the predominant antibody found in hen’s (Gallus domesticus egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli F4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT in laying hens intramuscularly immunized with E. coli F4. Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA. Secretory and serum immunoglobulin A (IgA were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer’s patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by

  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. Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses.

    Science.gov (United States)

    Velaga, Sarvari; Herbrand, Heike; Friedrichsen, Michaela; Jiong, Tian; Dorsch, Martina; Hoffmann, Matthias W; Förster, Reinhold; Pabst, Oliver

    2009-03-01

    Solitary intestinal lymphoid tissue (SILT) comprises a spectrum of phenotypically diverse lymphoid aggregates interspersed throughout the small intestinal mucosa. Manifestations of SILT range from tiny lymphoid aggregates almost void of mature lymphocytes to large structures dominated by B cells. Large SILT phenotypically resemble a single Peyer's patch follicle, suggesting that SILT might contribute to intestinal humoral immune responses. In this study, we track the fate of individual SILT in vivo over time and analyze SILT formation and function in chemokine receptor CXCR5-deficient mice. We show that, in analogy to Peyer's patches, formation of SILT is invariantly determined during ontogeny and depends on CXCR5. Young CXCR5-deficient mice completely lack SILT, suggesting that CXCR5 is essential for SILT formation during regular postnatal development. However, microbiota and other external stimuli can induce the formation of aberrant SILT distinguished by impaired development of B cell follicles in CXCR5-deficient mice. Small intestinal transplantation and bone marrow transplantation reveal that defect follicle formation is due to impaired B cell homing. Moreover, oral immunization with cholera toxin or infection with noninvasive Salmonella fail to induce efficient humoral immune responses in CXCR5-deficient mice. Bone marrow transplantation of CXCR5-deficient recipients with wild-type bone marrow rescued B cell follicle formation in SILT but failed to restore full humoral immune responses. These results reveal an essential role of CXCR5 in Peyer's patch and SILT development and function and indicate that SILT do not fully compensate for the lack of Peyer's patches in T cell-dependent humoral immune responses.

  8. 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.

  9. Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue

    Directory of Open Access Journals (Sweden)

    Specht Anke

    2010-01-01

    Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 Vpu protein degrades CD4 and counteracts a restriction factor termed tetherin (CD317; Bst-2 to enhance virion release. It has been suggested that both functions can be genetically separated by mutation of a serine residue at position 52. However, recent data suggest that the S52 phosphorylation site is also important for the ability of Vpu to counteract tetherin. To clarify this issue, we performed a comprehensive analysis of HIV-1 with a mutated casein kinase-II phosphorylation site in Vpu in various cell lines, primary blood lymphocytes (PBL, monocyte-derived macrophages (MDM and ex vivo human lymphoid tissue (HLT. Results We show that mutation of serine 52 to alanine (S52A entirely disrupts Vpu-mediated degradation of CD4 and strongly impairs its ability to antagonize tetherin. Furthermore, casein-kinase II inhibitors blocked the ability of Vpu to degrade tetherin. Overall, Vpu S52A could only overcome low levels of tetherin, and its activity decreased in a manner dependent on the amount of transiently or endogenously expressed tetherin. As a consequence, the S52A Vpu mutant virus was unable to replicate in macrophages, which express high levels of this restriction factor. In contrast, HIV-1 Vpu S52A caused CD4+ T-cell depletion and spread efficiently in ex vivo human lymphoid tissue and PBL, most likely because these cells express comparably low levels of tetherin. Conclusion Our data explain why the effect of the S52A mutation in Vpu on virus release is cell-type dependent and suggest that a reduced ability of Vpu to counteract tetherin impairs HIV-1 replication in macrophages, but not in tissue CD4+ T cells.

  10. CXCR4-tropic HIV-1 suppresses replication of CCR5-tropic HIV-1 in human lymphoid tissue by selective induction of CC-chemokines.

    Science.gov (United States)

    Ito, Yoshinori; Grivel, Jean-Charles; Chen, Silvia; Kiselyeva, Yana; Reichelderfer, Patricia; Margolis, Leonid

    2004-02-01

    In infected individuals, human immunodeficiency virus type 1 (HIV-1) exist as a "swarm" of quasi species compartmentalized in tissues where individual viral variants may interact locally. We have used human lymphoid tissue, where the critical events of HIV disease occur, to study local interactions in model HIV-1 binary swarms ex vivo. We infected tissue blocks with binary mixtures consisting either of CCR5-dependent and CXCR4-dependent variants or of 2 dual-tropic HIV-1 variants, of which one is skewed to utilization of CXCR4 and the other of CCR5. HIV-1 variants that use CXCR4 suppress replication of CCR5-dependent HIV-1 variants, whereas CCR5-dependent HIV-1 variants do not affect replication of CXCR4-dependent HIV-1. CC-chemokines that inhibit replication of CCR5-dependent HIV-1 variants were up-regulated by CXCR4-dependent HIV-1, thus possibly contributing to this suppression. Tissue-specific chemokine/cytokine network modulations triggered by individual HIV-1 variants may be an important mechanism of local interactions among HIV-1 quasi species in infected tissue.

  11. Epstein-barr virus-associated extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma) arising in the parotid gland of a child with ataxia telangiectasia.

    Science.gov (United States)

    Bennett, Jennifer A; Bayerl, Michael G

    2015-03-01

    Hematologic malignancies, in particular T-cell lymphomas/leukemias, are prevalent in patients with ataxia telangiectasia (AT), with most reported cases being clinically aggressive and high grade. Epstein-Barr virus (EBV) is often associated with lymphoid proliferations/neoplasms arising in immunodeficient patients. Reports of low-grade B-cell neoplasms in the ataxia telangiectasia population are extremely rare. Here, we describe a case of EBV-associated extranodal marginal zone lymphoma (mucosa-associated lymphoid tissue lymphoma) of the parotid gland in a 16-year-old boy with AT. In addition, we review the literature of hematologic malignancies in the AT population as well as the occurrence of EBV in mucosa-associated lymphoid tissue lymphoma.

  12. Co-occurrence of papillary thyroid carcinoma and mucosa-associated lymphoid tissue lymphoma in a patient with long-standing hashimoto thyroiditis.

    Science.gov (United States)

    Nam, Yoon Jeong; Kim, Bo Hyun; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

    2013-12-01

    Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies.

  13. Primary B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma of the Hard Palate and Parotid Gland: Report of One Case and Review of the Literature

    Science.gov (United States)

    Yonal-Hindilerden, Ipek; Hindilerden, Fehmi; Arslan, Serkan; Turan-Guzel, Nalan; Dogan, Ibrahim Oner; Nalcaci, Meliha

    2016-01-01

    A 61-year-old woman was admitted to our hospital with an ulcerated palate mass and swelling of the right parotid gland. Incisional biopsy from the hard palate revealed an extranodal marginal zone B-cell lymphoma, also called mucosa-associated lymphoid tissue (MALT) lymphoma. Final diagnosis was MALT lymphoma of the parotid gland with concomitant involvement of an extremely seldom site of involvement: the hard palate. To our knowledge, this report illustrates the first case of MALT lymphoma of the hard palate and parotid gland without an underlying autoimmune disease. Rituximab-based combination regimen (R-CHOP) provided complete remission with total regression of mass lesions at the hard palate and parotid gland. At 44-month follow-up, there is no disease relapse. We adressed the manifestations and management of MALT lymphoma patients with involvement of salivary gland and oral cavity. PMID:27738485

  14. 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.

  15. Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells.

    Science.gov (United States)

    Galloway, Nicole L K; Doitsh, Gilad; Monroe, Kathryn M; Yang, Zhiyuan; Muñoz-Arias, Isa; Levy, David N; Greene, Warner C

    2015-09-01

    The progressive depletion of CD4 T cells underlies clinical progression to AIDS in untreated HIV-infected subjects. Most dying CD4 T cells correspond to resting nonpermissive cells residing in lymphoid tissues. Death is due to an innate immune response against the incomplete cytosolic viral DNA intermediates accumulating in these cells. The viral DNA is detected by the IFI16 sensor, leading to inflammasome assembly, caspase-1 activation, and the induction of pyroptosis, a highly inflammatory form of programmed cell death. We now show that cell-to-cell transmission of HIV is obligatorily required for activation of this death pathway. Cell-free HIV-1 virions, even when added in large quantities, fail to activate pyroptosis. These findings underscore the infected CD4 T cells as the major killing units promoting progression to AIDS and highlight a previously unappreciated role for the virological synapse in HIV pathogenesis.

  16. Diffuse Large B-Cell Lymphoma Transformed from Mucosa-Associated Lymphoid Tissue Lymphoma Arising in a Female Urethra Treated with Rituximab for the First Time

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    A. Al Zahrani

    2012-05-01

    Full Text Available A 30-year-old female patient presented to the gynecology clinic with a small (painless swelling at the urethral orifice. She underwent surgical excision of the lesion. Pathological examination revealed non-Hodgkin’s lymphoma of diffuse large B-cell type and mucosa-associated lymphoid tissue type, stage IE. The patient refused radiotherapy. Accordingly, we started CHOP-R chemotherapy. She received a total of 6 cycles of CHOP and 8 cycles of rituximab. Patient follow-up was done 3 months later through CT scan and cytoscopy confirming the complete remission. The patient has been disease-free for 4 years. We reviewed 26 cases of this rare entity reported previously.

  17. Primary non-Hodgkin′s lymphoma of the salivary gland: A spectrum of lymphoepithelial sialadenitis, low-grade B-cell lymphoma of mucosa-associated lymphoid tissue with transformation to high-grade lymphoma

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    Agale Shubhangi

    2010-04-01

    Full Text Available Lymphoid infiltrates of the salivary gland can be either reactive or neoplastic. The reactive lesion, lymphoepithelial sialadenitis (LESA may be associated with Sjogren′s syndrome (SS or may occur as an isolated salivary gland enlargement. Patients with LESA/SS have a particularly high risk of subsequently developing lymphoma, which is a low-grade mucosa-associated lymphoid tissue (MALT type lymphoma of the salivary gland. We document a rare case of primary non-Hodgkin′s lymphoma of the parotid gland arising in the background of LESA and with a rare example of transformation from low grade to high-grade B cell lymphoma of MALT type.

  18. Detection of Foot-and-mouth Disease Virus RNA and Capsid Protein in Lymphoid Tissues of Convalescent Pigs Does Not Indicate Existence of a Carrier State.

    Science.gov (United States)

    Stenfeldt, C; Pacheco, J M; Smoliga, G R; Bishop, E; Pauszek, S J; Hartwig, E J; Rodriguez, L L; Arzt, J

    2016-04-01

    A systematic study was performed to investigate the potential of pigs to establish and maintain persistent foot-and-mouth disease virus (FMDV) infection. Infectious virus could not be recovered from sera, oral, nasal or oropharyngeal fluids obtained after resolution of clinical infection with any of five FMDV strains within serotypes A, O and Asia-1. Furthermore, there was no isolation of live virus from tissue samples harvested at 28-100 days post-infection from convalescent pigs recovered from clinical or subclinical FMD. Despite lack of detection of infectious FMDV, there was a high prevalence of FMDV RNA detection in lymph nodes draining lesion sites harvested at 35 days post-infection, with the most frequent detection recorded in popliteal lymph nodes (positive detection in 88% of samples obtained from non-vaccinated pigs). Likewise, at 35 dpi, FMDV capsid antigen was localized within follicles of draining lymph nodes, but without concurrent detection of FMDV non-structural protein. There was a marked decline in the detection of FMDV RNA and antigen in tissue samples by 60 dpi, and no antigen or viral RNA could be detected in samples obtained at 100 dpi. The data presented herein provide the most extensive investigation of FMDV persistence in pigs. The overall conclusion is that domestic pigs are unlikely to be competent long-term carriers of infectious FMDV; however, transient persistence of FMDV protein and RNA in lymphoid tissues is common following clinical or subclinical infection.

  19. Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo

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    Sertel Serkan

    2009-01-01

    Full Text Available Abstract Background HIV-1 Nef critically contributes to AIDS in part by augmenting virus titers in infected individuals. Analyzing which of Nef's activities contribute to HIV pathogenesis has been hampered by the lack of a cell culture model in which Nef exerts pronounced effects on HIV replication. The human lymphoid aggregate culture (HLAC from tonsil maintains the cell populations and cytokine milieu found in vivo, supports a productive infection without exogenous stimulation, and Nef contributes to efficient HIV-1 replication as well as CD4+ T cell depletion in this experimental ex vivo-model. Results To identify determinants in Nef that mediate these activities, we infected HLAC with a panel of isogenic HIV-1NL4-3 strains that encode for well-characterized mutants of HIV-1SF2 Nef. Determination of HIV-1 replication revealed that enhancement of the virus spread by Nef is governed by a complex set of protein interaction surfaces. In contrast, increased CD4+ T lymphocyte depletion depended on only two protein interaction surfaces in Nef that mediate either downregulation of cell surface CD4 or interaction with the NAKC signalosome. Consistently, in HLAC from 9 out of 14 donors, Nef enhanced CD4+ T cell depletion in the absence of a significant effect on virus replication. Moreover, our results suggest that this Nef-dependent enhancement in depletion occurred predominately in uninfected bystander CD4+ T cells. Conclusion Our findings suggest that Nef facilitates depletion of CD4+ T lymphocytes in HIV-1-infected lymphoid tissue ex vivo by increasing the pool of productively infected cells and by sensitizing bystander cells for killing. This ability might contribute to Nef's pathogenic potential in vivo.

  20. Cytopathicity of Human Immunodeficiency Virus Type 2 (HIV-2) in Human Lymphoid Tissue Is Coreceptor Dependent and Comparable to That of HIV-1

    Science.gov (United States)

    Schramm, Birgit; Penn, Michael L.; Palacios, Emil H.; Grant, Robert M.; Kirchhoff, Frank; Goldsmith, Mark A.

    2000-01-01

    Epidemiological studies have shown that human immunodeficiency virus type 2 (HIV-2) is markedly less pathogenic than HIV-1 in vivo. Individuals infected with HIV-2 exhibit a remarkably slow rate of disease development, and these clinical properties have been attributed presumptively to an “attenuated” phenotype of HIV-2 itself. Here, we investigated the impact of coreceptor usage on the cytopathicity of HIV-2 and compared its pathogenic potential with that of HIV-1 in a unique human lymphoid histoculture model. We found that HIV-2 strains, as well as closely related simian immunodeficiency viruses (SIV), displayed mildly or highly aggressive cytopathic phenotypes depending on their abilities to use the coreceptor CCR5 or CXCR4, respectively. A side-by-side comparison of primary X4 HIV-1 and HIV-2 strains revealed similar, high degrees of cytopathicity induced by both HIV types. Furthermore, we found that HIV-2 coreceptor specificity for CCR5 and CXCR4 determined the target cell population for T-cell depletion in lymphoid tissue. Finally, utilization of the alternate coreceptors BOB and Bonzo did not significantly increase the cytopathic properties of HIV-2. These findings demonstrate that coreceptor preference is a key regulator of target cell specificity and the cytopathic potential of HIV-2, with indistinguishable rules compared with HIV-1. Moreover, HIV-2 strains are not characterized by an intrinsically lower cytopathicity than HIV-1 strains. Therefore, direct cytopathic potential per se does not explain the unique behavior of HIV-2 in people, highlighting that other unknown factors need to be elucidated as the basis for their lesser virulence in vivo. PMID:11000231

  1. Mucosa-associated lymphoid tissue in individuals with AIDS Tecido linfoide associado à mucosa em indivíduos com AIDS

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    Janainna Grazielle Pacheco Olegario

    2011-06-01

    Full Text Available Vestibular folds (VF protect upper airways, but contain fewer immune cells in AIDS patients, which affects the structure of lymphoid follicles (LF. OBJECTIVE: To characterize fibrosis and immunoglobulin production in vestibular fold lymphoid tissues of AIDS patients with or with no infection and malnutrition. MATERIALS AND METHODS: A retrospective study of 71 adult vestibular fold autopsy specimens. The morphological analysis was done using the picrosirius staining method. Immunohistochemical methods consisted of anti-IgA, anti IgG, and anti IgM antibodies. RESULTS: Fibrosis was less intense in AIDS patients compared to subjects without AIDS; the same applied to patients with infection or malnutrition. IgA and IgG titers were higher in AIDS patients; IgM titers were higher in cases with infection. CONCLUSION: This study helps understand variations in lymphoid follicle components of AIDS patients; it also shows the influence of architectural changes and the effect of associated respiratory infection and malnutrition on lymphoid follicle function.Pregas vestibulares (PV são responsáveis pela proteção das vias aéreas superiores e, nos indivíduos com AIDS, apresenta diminuição das células imunes, o que influencia na estrutura dos folículos linfoides (FL. OBJETIVO: Caracterizar a fibrose e a produção de imunoglobulinas nos FL das PV nos indivíduos com AIDS, com e sem infecções e subnutrição associadas. MATERIAIS E MÉTODOS: Foi realizado um estudo retrospectivo transversal em 71 PV de adultos autopsiados. Para a análise morfológica foi usada a coloração picro-sirius. A imuno-histoquímica foi realizada com os anticorpos: anti-IgA, anti-IgG, anti-IgM. RESULTADOS: Nos pacientes com AIDS, a quantidade de fibrose foi menor quando comparados com aqueles que não possuíam AIDS, o mesmo sendo encontrado nos pacientes com infecções ou subnutrição. As quantidades de IgA e IgG foram maiores nos indivíduos com AIDS, e os valores de Ig

  2. Impact of coccidial infection on vaccine- and vvIBDV in lymphoid tissues of SPF chickens as detected by RT-PCR

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    Bisgaard Magne

    2006-09-01

    Full Text Available Abstract Background This study aimed at investigating a potential effect caused by coccidia on the immune response to vaccine- and very virulent infectious bursal disase virus (vvIBDV in SPF chickens. Methods Two groups of three weeks old SPF chickens were vaccinated prior to inoculation with coccidia and challenge with virulent IBDV, all within a period of eight days. Two control groups were similarly treated, except that challenge with field virus was omitted in one group while inoculation with coccidia was omitted in the other group. Clinical signs, lesions in the intestines caused by coccidia, lesions in the bursa of Fabricius caused by IBDV, IBDV-antibody titres, and virus detection by reverse transcription polymerase chain reaction (RT-PCR were compared among the groups. Lymphoid tissues and swab samples were analysed by general RT-PCR, and positive results were identified by strain specific duplex (DPX RT-PCR. Results In the tripple-infected groups, vaccine strain IBDV was detected in spleen and thymus tissues, and no field virus was detected in bursa samples, contrary to the double-infected groups. Conclusion The results suggest an enhancing effect on the immune response caused by subclinical coccidiosis and vvIBDV acting in concert.

  3. 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.

  4. Acute infection with bovine viral diarrhea virus of low or high virulence leads to depletion and redistribution of WC1(+) γδ T cells in lymphoid tissues of beef calves.

    Science.gov (United States)

    Palomares, Roberto A; Sakamoto, Kaori; Walz, Heather L; Brock, Kenny V; Hurley, David J

    2015-10-15

    The objective of this study was to determine the abundance and distribution of γδ T lymphocytes in lymphoid tissue during acute infection with high (HV) or low virulence (LV) non-cytopathic bovine viral diarrhea virus (BVDV) in beef calves. This study was performed using tissue samples from a previous experiment in which thirty beef calves were randomly assigned to 1 of 3 groups: LV [n=10; animals inoculated intranasally (IN) with LV BVDV-1a (strain SD-1)], HV [n=10; animals inoculated IN with HV BVDV-2 (strain 1373)], and control (n=10; animals inoculated with cell culture medium). On day 5 post inoculation, animals were euthanized, and samples from spleen and mesenteric lymph nodes (MLN) were collected to assess the abundance of WC1(+) γδ T cells. A higher proportion of calves challenged with BVDV showed signs of apoptosis and cytophagy in MLN and spleen samples compared to the control group. A significantly lower number of γδ T cells was observed in spleen and MLN from calves in HV and LV groups than in the control calves (P<0.05). In conclusion, acute infection with HV or LV BVDV resulted in depletion of WC1(+) γδ T cells in mucosal and systemic lymphoid tissues at five days after challenge in beef calves. This reduction in γδ T cells in the studied lymphoid tissues could be also due to lymphocyte trafficking to other tissues.

  5. Validation of use of rectoanal mucosa-associated lymphoid tissue for immunohistochemical diagnosis of chronic wasting disease in white-tailed deer (Odocoileus virginianus).

    Science.gov (United States)

    Keane, Delwyn; Barr, Daniel; Osborn, Rebecca; Langenberg, Julie; O'Rourke, Katherine; Schneider, David; Bochsler, Philip

    2009-05-01

    The examination of rectoanal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens for the diagnosis of transmissible spongiform encephalopathies has been described in sheep, elk, and small numbers of mule and white-tailed deer. Previous sample numbers have been too small to validate examination of this type of tissue as a viable antemortem diagnostic test. In this study, we examined RAMALT collected postmortem from 76 white-tailed deer removed from a farm in Wisconsin known to be affected by chronic wasting disease (CWD) and from 210 free-ranging white-tailed deer harvested from an area in Wisconsin where the overall prevalence of CWD among the deer was approximately 4 to 6%. The results of immunohistochemical (IHC) staining of the RAMALT sections were compared to the results of IHC staining of sections from the brain stem at the convergence of the dorsal motor nucleus of the vagus nerve, sections of the medial retropharyngeal lymph nodes (RLNs), and sections of tonsil (sections of tonsil only from captive animals were tested). The sensitivities of the IHC staining test with RAMALT sections were 81% for the captive animals and 91% for the free-ranging animals. False-negative results were usually associated with early infection, indicated by a low intensity of immunostaining in the obex and/or a polymorphism at PRNP codon 96. While the RLN remains the tissue of choice for use for the diagnosis of CWD in white-tailed deer, the results of the present study further support the use of RAMALTs collected antemortem as an adjunct to testing of tonsil biopsy specimens and surveillance by necropsy for the screening of farmed deer which have been put at risk through environmental exposure or exposure to deer with CWD.

  6. Successful treatment of mucosa-associated lymphoid tissue lymphoma in a patient with gastric and rectal lesions with metachronous and ectopic development

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    Hajime Umezu

    2011-04-01

    Full Text Available A 75-year-old female, who had an abnormal stomach x-ray finding, was admitted to the hospital for further examination and therapy. Upper GI endoscopy showed reddish and swollen folds on the greater curvature of the gastric body and a biopsy was of this lesion revealed malignant lymphoma (small cell type or mucosa-associated lymphoid tissue (MALT lymphoma suspected. The patient was infected with Helicobacter pylori (H. pylori, however, in response to the patient’s wishes, a total gastrectomy, omentectomy and splenectomy were performed and the histological diagnosis was gastric MALT lymphoma. Two courses of CHOP therapy (cyclophosphamide (CPM 750 mg/m2/day, day 1, adriamycin (ADM 50 mg/m2/day, day 1, vincristine sulfate (VCR 1.4 mg/m2/day, day 1, prednisolone 100 mg/body, day 1-5 were administered as adjuvant chemotherapy. A colonoscopic examination performed about 4.5 yr after the operation revealed rectal submucosal tumors and the biopsied specimens were diagnosed as malignant lymphoma. A transanal focal resection was performed and the histological diagnosis was metachronous and ectopic development of MALT lymphoma. The histological finding was similar to the gastric lesion. About 4 and 7 yr after the first development of rectal MALT lymphoma, MALT lymphomas developed repeatedly in the rectal lesion, however, these were resected repeatedly and no developmenthas occurred during the past two years. This report presents a very rare case of metachronous and ectopic MALT lymphoma de

  7. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

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    María Eugenia Hernandez

    2013-01-01

    Full Text Available 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. Inhibition of TGF-β and EGF pathway gene expression and migration of oral carcinoma cells by mucosa-associated lymphoid tissue 1.

    Science.gov (United States)

    Ohyama, Y; Kawamoto, Y; Chiba, T; Maeda, G; Sakashita, H; Imai, K

    2013-07-09

    Expression of mucosa-associated lymphoid tissue 1 (MALT1) is inactivated in oral carcinoma patients with worse prognosis. However, the role in carcinoma progression is unknown. Unveiling genes under the control of MALT1 is necessary to understand the pathology of carcinomas. Gene data set differentially transcribed in MALT1-stably expressing and -marginally expressing oral carcinoma cells was profiled by the microarray analysis and subjected to the pathway analysis. Migratory abilities of cells in response to MALT1 were determined by wound-healing assay and time-lapse analysis. Totally, 2933 genes upregulated or downregulated in MALT1-expressing cells were identified. The subsequent pathway analysis implicated the inhibition of epidermal growth factor and transforming growth factor-β signalling gene expression, and highlighted the involvement in the cellular movement. Wound closure was suppressed by wild-type MALT1 (66.4%) and accelerated by dominant-negative MALT1 (218.6%), and the velocities of cell migration were increased 0.2-fold and 3.0-fold by wild-type and dominant-negative MALT1, respectively. These observations demonstrate that MALT1 represses genes activating the aggressive phenotype of carcinoma cells, and suggest that MALT1 acts as a tumour suppressor and that the loss of expression stimulates oral carcinoma progression.

  9. Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH17 cytokine interleukin-22

    Science.gov (United States)

    Hughes, Tiffany; Becknell, Brian; McClory, Susan; Briercheck, Edward; Freud, Aharon G.; Zhang, Xiaoli; Mao, Hsiaoyin; Nuovo, Gerard; Yu, Jianhua

    2009-01-01

    Considerable functional heterogeneity within human natural killer (NK) cells has been revealed through the characterization of distinct NK-cell subsets. Accordingly, a small subset of CD56+NKp44+NK cells, termed NK-22 cells, was recently described within secondary lymphoid tissue (SLT) as IL-22− when resting, with a minor fraction of this population becoming IL-22+ when activated. Here we discover that the vast majority of stage 3 immature NK (iNK) cells in SLT constitutively and selectively express IL-22, a TH17 cytokine important for mucosal immunity, whereas earlier and later stages of NK developmental intermediates do not express IL-22. These iNK cells have a surface phenotype of CD34−CD117+CD161+CD94−, largely lack expression of NKp44 and CD56, and do not produce IFN-γ or possess cytolytic activity. In summary, stage 3 iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, and IL-22 protein production, but do not express IL-17A or IL-17F. PMID:19244159

  10. 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. PMID:23533999

  11. B-cell subpopulations from normal human secondary lymphoid tissues with specific gene expression profiles and phenotypes

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Schmitz, Alexander; Perez Andres, Martin

    included homogenization, isolation of mononuclear cells, MFC and FACS sorting using multicolour fluorescence single tube panels.of antibodies against surface molecules as CD10/20/27/38/45, supplemented with tissue related antibodies. Isolated B-cell subpopulations were evaluated by morphological inspection......, naïve, centroblast, centrocyte, memory, and plasmablasts. The identity of the tonsillar subpopulations was verified using qRT-PCR and exon microarray GEP based on the used discriminative phenotypic markers as well as transcriptions factors BACH2, BCL6, PAX5, IRF4, P27, PRDM1 and XBP1. Globally, the B...

  12. B-cell subpopulations from normal human secondary lymphoid tissues with specific gene expression profiles and phenotypes

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Schmitz, Alexander; Perez Andres, Martin;

    In order to improve insights into the B-cell biology and thereby B-cell myelomagenesis we have established a MSCNET standard for multiparametric flow cytometry (MFC) and cell sorting (FACS) for subsequent genetic analysis. The material analysed was fresh tonsils, blood and bone marrow. The method...... included homogenization, isolation of mononuclear cells, MFC and FACS sorting using multicolour fluorescence single tube panels.of antibodies against surface molecules as CD10/20/27/38/45, supplemented with tissue related antibodies. Isolated B-cell subpopulations were evaluated by morphological inspection...... and single gene expression analysis (qRT-PCR) for transcription factors as well as global gene expression profiling (GEP; GeneChip Human Exon 1.0 ST Array). For example for tonsils, based on the immunophenotypic presentation (including CD3/44/CXCR4 in the panel), B-cell subsets were identified and sorted...

  13. 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.

  14. 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.

  15. Characterization of lymphocyte subsets over a 24-hour period in Pineal-Associated Lymphoid Tissue (PALT in the chicken

    Directory of Open Access Journals (Sweden)

    McNulty John A

    2006-01-01

    Full Text Available Abstract Background Homeostatic trafficking of lymphocytes in the brain has important relevance to the understanding of CNS disease processes. The pineal gland of the chicken contains large accumulations of lymphocytes that suggest an important role related to homeostatic circadian neuro-immune interactions. The purpose of this initial study was to characterize the lymphocyte subsets in the pineal gland and quantitate the distribution and frequency of lymphocyte phenotypes at two time points over the 24-hour light:dark cycle. Results PALT comprised approximately 10% of the total pineal area. Image analysis of immunocytochemically stained sections showed that the majority of lymphocytes were CD3+ (80% with the remaining 20% comprising B-cells and monocytes (Bu-1+, which tended to distribute along the periphery of the PALT. T-cell subsets in PALT included CD4+ (75–80%, CD8+ (20–25%, TCRαβ/Vβ1+ (60%, and TCRγδ+ (15%. All of the T-cell phenotypes were commonly found within the interfollicular septa and follicles of the pineal gland. However, the ratios of CD8+/CD4+ and TCRγδ+/TCRαβ/Vβ1+ within the pineal tissue were each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+ and TCRγδ+/TCRαβ/Vβ1+ each approximated 1:4. Bu-1+ cells were only rarely seen in the pineal interstitial spaces, but ramified Bu-1+ microglia/macrophages were common in the pineal follicles. Effects of the 24-h light:dark cycle on these lymphocyte-pineal interactions were suggested by an increase in the area of PALT, a decline in the density of TCRαβ/Vβ1+ cells, and a decline in the area density of Bu-1+ microglia at the light:dark interphase (1900 h compared to the dark:light interphase (0700 h. Conclusion The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of neuro-immune interactions in this part of the brain. Our results further suggest that these interactions have a temporal component related to the 24-hour light

  16. Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ken, E-mail: keharada@ncc.go.jp [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Suzuki, Shigenobu [Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo (Japan); Tobinai, Kensei [Department of Hematologic Oncology, National Cancer Center Hospital, Tokyo (Japan); Uno, Takashi [Department of Radiology, Chiba University School of Medicine, Chiba (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2014-03-01

    Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

  17. Long-Term Outcome and Patterns of Failure in Primary Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Naoki [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan); Sasaki, Ryohei, E-mail: rsasaki@med.kobe-u.ac.jp [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan); Nishimura, Hideki; Yoshida, Kenji; Miyawaki, Daisuke; Nakayama, Masao; Uehara, Kazuyuki; Okamoto, Yoshiaki; Ejima, Yasuo [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan); Azumi, Atsushi [Division of Ophthalmology, Kobe University Graduate School of Medicine, Hyogo (Japan); Matsui, Toshimitsu [Division of Hematology, Kobe University Graduate School of Medicine, Hyogo (Japan); Sugimura, Kazuro [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan)

    2012-03-15

    Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.

  18. 49例MALT淋巴瘤临床资料分析%Analysis of Prognostic Correlated Factors of 49 Patients with Mucosa-associated Lymphoid Tissue Lymphoma

    Institute of Scientific and Technical Information of China (English)

    景红梅; 克晓燕; 董菲

    2007-01-01

    本研究旨在探讨黏膜相关淋巴组织淋巴瘤(mucosa-associated lymphoid tissue lymphoma,MALT lymphoma)临床特点、API2-MALT1基因的表达与预后的关系.通过回顾临床资料,研究我院49例MALT淋巴瘤患者的临床特点,并通过RT-PCR法检测部分石蜡标本API2-MALT1基因重排.结果表明:MALT淋巴瘤患者的发病平均年龄为52.4岁,50岁以上的患者占67.4%,肿瘤多发生在胃肠道,其次在甲状腺;49例中Ⅰ、Ⅱ期患者占776.%,Ⅲ、Ⅳ期患者占22.4%;API2-MALT1基因重排在低度恶性组、转化组的阳性率分别为38.1%和12.5%;3年生存率为93.8%.结论:MALT淋巴瘤患者的临床进展缓慢,对化疗敏感,预后较好,可根据有无API2-MALT1基因重排选择不同的治疗方法,对Ⅰ期HP阳性患者可采用抗HP治疗.

  19. Primary Thymic Extranodal Marginal-Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type Exhibits Distinctive Clinicopathological and Molecular Features

    Science.gov (United States)

    Inagaki, Hiroshi; Chan, John K. C.; Ng, Josephine W. M.; Okabe, Mitsukuni; Yoshino, Tadashi; Okamoto, Masataka; Ogawa, Hiroshi; Matsushita, Hiroshi; Yokose, Tomoyuki; Matsuno, Yoshihiro; Nakamura, Naoya; Nagasaka, Tetsuro; Ueda, Ryuzo; Eimoto, Tadaaki; Nakamura, Shigeo

    2002-01-01

    Extranodal marginal-zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) arising in the thymus is rare, with the largest series in the literature including only three cases. In the present study, we investigated 15 cases of thymic MALT lymphoma to systematically characterize its clinical, histopathological, and molecular features. There was a marked female predilection (male:female = 1:4), with a mean age of 55 years at diagnosis. There was a strong association with autoimmune disease, especially Sjögren’s syndrome. Histologically, the thymic lymphoma showed the characteristic morphological features of extranodal MZBL of MALT type. Cysts were common. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating and expanding the Hassall’s corpuscles and epithelium lining the cysts. Plasmacytic differentiation was apparent in all cases. Notably, 13 of 15 cases expressed immunoglobulin (Ig) A phenotype; IgA expression in thymic MALT lymphoma was in striking contrast with the IgM phenotype observed in most of the Sjögren’s syndrome-associated MZBLs and MALT lymphomas at other sites. Epstein-Barr virus was absent, and API2-MALT1 gene fusion, a recently reported MALT lymphoma-specific gene abnormality, was not detected in any case. Although one patient died of disease 85 months after the diagnosis, other patients were alive with overall 3-year and 5-year survival rates being 89% and 83%, respectively. Among the 22 patients reported previously and in the present series, at least 17 patients (77%) were Asians. These data indicate that thymic MALT lymphoma may represent a distinct subgroup of MALT lymphoma characterized by apparent predilection for Asians, a strong association with autoimmune disease, frequent presence of cysts, consistent plasma cell differentiation, tumor cells expressing IgA phenotype, and consistent lack of API2-MALT1 gene fusion. PMID:11943727

  20. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Adam J., E-mail: adam_olszewski@brown.edu; Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  1. Ultrastructural Pathologic Observation on the Gut-Associated Lymphoid Tissues of Sacculus Rotundus of Rabbits Infected with Rabbit Haemorrhagic Disease Virus

    Institute of Scientific and Technical Information of China (English)

    SHE Rui-ping; YANG Han-chun; JIA Jun-zheng; LIU Hai-hong; MA Yi-xin; Itakura C

    2003-01-01

    Ultrastructural pathological changes in the gut-associated lymphoid tissues of sacculus rotundus(SR) of rabbits infected with rabbit haemorrhagic disease virus (RHDV) were first observed. There were nu-merous holes at the luminal and basement membrane surfaces of the dome epithelium(DE), consistently ac-companied by necrosis of lymphocytes and M-cells, and pronounced depletion of lymphocytes in the domes andfollicles, decrease of DE complex with formation of pseudomembranous structure on the surface of the domeepithelium. A specific finding in lymphocytes and macrophages was that severe destruction detraction of themembrane of rough endoplasmic reticulum(RER) was accompanied by conspicious increase of solitary, ribo-some-like particles in the cytoplasm, with appearances of intranuclear particles and intranuclear inclusions. Itwas found that there were many round and dense virion-like particles, with 26 nm in diameter, in the nucleiand cytoplasm of lymphoctes, plasma cells, macrophages and fibroblasts, or in degenerated cells and cellulardebris. At the same time, another round virion-like particles about 34 nm in diameter were also seen in the cy-toplasm of some cells and interstitium. The results indicated that the appearances of the ribosome-like parti-cles, virion-like particles and inclusion bodies were related to the replication and assembly of RHDV. Thepresent observations suggested that DE of sacculus rotundus could be a open pathway and a transporting routefor the entry of antigens into hosts. While the antigen is profoundly deleterious, DE may be as a closed portalor a barrier preventing the foreign antigenic materials from invading.

  2. Immunohistochemical comparison of CD5, lambda, and kappa expression in primary and recurrent buccal mucosa-associated lymphoid tissue (MALT) lymphomas.

    Science.gov (United States)

    Tanaka, Toshiaki; Kitabatake, Kenichirou; Iino, Mituyoshi; Goto, Kaoru

    2011-09-06

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's lymphoma.Primary MALT lymphomas can also occur in the oral cavity, although their appearance in this location is rare. The neoplastic cells of which MALT lymphomas are composed express B-cell antigens and show monotypic immunoglobulin expression with light-chain restriction.Although neoplastic MALT lymphoma cells do not express CD5, previous studies have shown that CD5 positive MALT lymphomas are more prone to dissemination than those that do not express CD5. Moreover, there are some reports that describe kappa- and lambda- dual light chain expression in B cell malignant neoplasms.A 66-year-old Japanese woman with swelling of the right buccal mucosa was referred to our hospital. The lesion was excised and was pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21) chromosome translocation.Swelling of the right buccal mucosa recurred 2 years later. The recurrent tumor was then excised and pathologically diagnosed as MALT lymphoma.Immunohistochemical examination of CD5, lambda, and kappa expressions revealed that the primary tumor was positive for CD5, kappa, and lambda, but the recurrent tumor was weakly positive for CD5 and kappa.With respect to lambda positivity, the recurrent tumor showed negativity.Our study suggests that immunohistochemical expression of CD5, kappa, and lambda in oral MALT lymphoma have the risk of recurrence.We first described the recurrence of CD5 positive MALT lymphoma in the oral cavity and compared the immunohistochemical expressions of CD5, lambda, and kappa between the primary and recurrent tumors.

  3. Conjunctiva-associated lymphoid tissue (CALT reactions to antiglaucoma prostaglandins with or without BAK-preservative in rabbit acute toxicity study.

    Directory of Open Access Journals (Sweden)

    Hong Liang

    Full Text Available Conjunctiva-associated lymphoid tissue (CALT is closely associated with ocular surface immunity. This study investigated the effects of antiglaucoma prostaglandin analogs with or without benzalkonium chloride (BAK preservative on organized CALT using an acute toxic model. A total of 48 albino rabbits were used and seven groups of treatments were constituted. Solutions (50 µl of PBS, 0.02%BAK, (0.02%BAK+latanoprost, (0.015%BAK+travoprost, (0.005%BAK+bimatoprost, (BAK-freetravoprost preserved with the SofZia® system or (BAK-freetafluprost were instilled 15 times at 5-min intervals in both eyes. CALT changes were analyzed using in vivo confocal microscopy (IVCM, immunohistology in cryosections for detecting MUC-5AC+ mucocytes and CD45+ hematopoietic cells. Antiglaucoma eye drops stimulated inflammatory cell infiltration in the CALT, and seemed to be primarily related to the concentration of their BAK content. The CALT reaction after instillation of BAK-containing eye drops was characterized by inflammatory cell infiltration in the dome and intrafollicular layers and by cell circulation inside the lymph vessels. CD45 was strongly expressed in the CALT after instillation of all BAK-containing solutions at 4 h and decreased at 24 h. The number of MUC-5AC+ mucocytes around the CALT structure decreased dramatically after instillation of BAK-containing solutions. This study showed for the first time the in vivo aspect of rabbit CALT after toxic stimuli, confirming the concentration-dependent toxic effects of BAK. IVCM-CALT analysis could be a pertinent tool in the future for understanding the immunotoxicologic challenges in the ocular surface and would provide useful criteria for evaluating newly developed eye drops.

  4. 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.

  5. 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

  6. 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

  7. Interactions between gut-associated lymphoid tissue and colonization levels of indigenous, segmented, filamentous bacteria in the small intestine of mice

    NARCIS (Netherlands)

    Snel, J; Hermsen, CC; Bos, NA; Eling, WMC; Cebra, JJ; Heidt, PJ; Smits, H.J.

    1998-01-01

    Unlike most other indigenous bacteria, segmented filamentous bacteria (SFB) are potent activators of the mucosal immune system. SFB are strongly anchored to the epithelial cells of the small intestine where they have a preference for mucosal lymphoid epithelium. Since SFB are only present in high nu

  8. Identifiability, exchangeability and confounding revisited

    OpenAIRE

    Greenland, Sander; Robins, James Matthew

    2009-01-01

    In 1986 the International Journal of Epidemiology published "Identifiability, Exchangeability and Epidemiological Confounding". We review the article from the perspective of a quarter century after it was first drafted and relate it to subsequent developments on confounding, ignorability, and collapsibility.

  9. 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.

  10. Analysis of vacA, cagA, and IS605 Genotypes and Those Determined by PCR Amplification of DNA between Repetitive Sequences of Helicobacter pylori Strains Isolated from Patients with Nonulcer Dyspepsia or Mucosa-Associated Lymphoid Tissue Lymphoma

    OpenAIRE

    van Doorn, Nathalie E. M.; Namavar, Ferry; Doorn, Leen-Jan; Durrani, Zarmina; Kuipers, Ernst J; Vandenbroucke-Grauls, Christina M. J. E.

    1999-01-01

    The vacA s and m genotypes and the presence of cagA and IS605 were determined in Helicobacter pylori strains from patients with mono- and multiple infections. Surprisingly, these genetic markers were not associated with nonulcer dyspepsia or mucosa-associated lymphoid tissue lymphoma. The presence of cagA correlated with the presence of the vacA s1 allele (P < 0.05), whereas the presence of IS605 was associated with the presence of the s2 allele (P < 0.05).

  11. 黏膜相关淋巴组织淋巴瘤和凋亡相关基因%Mucosa-associated lymphoid tissue lymphoma and apoptosis-related gene

    Institute of Scientific and Technical Information of China (English)

    黄江海; 许淑媛

    2007-01-01

    细胞凋亡受抑是黏膜相关淋巴组织(mucosa-associated lymphoid tissue,MALT)淋巴瘤发生的重要机制.MALT淋巴瘤凋亡相关基因的研究逐渐引起了重视.API2-MALT1融合基因和bcl-10过表达分别激活NF-κB,以NF-κB激活为核心,涉及到p53,Fas,API2,MALT1等凋亡相关基因,导致细胞凋亡受抑.

  12. [Bias in observational research: 'confounding'].

    Science.gov (United States)

    Groenwold, Rolf H H

    2012-01-01

    Confounding is an important and common issue in observational (non-randomized) research on the effects of pharmaceuticals or exposure to etiologic factors (determinants). Confounding is present when a third factor, related to both the determinant and the outcome, distorts the causal relation between these two. There are different methods to control for confounding. The most commonly used are restriction, stratification, multivariable regression models, and propensity score methods. With these methods it is only possible to control for variables for which data is known: measured confounders. Research in the area of confounding is currently directed at the incorporation of external knowledge on unmeasured confounders, the evaluation of instrumental variables, and the impact of time-dependent confounding.

  13. 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.

  14. Clinical and prognostic characteristice of pulmonary mucosa-associated lymphoid tissue lymphoma:a retrospective analysis of 23 cases in a chinese population

    Institute of Scientific and Technical Information of China (English)

    HUANG Hui; LU Zhi-wei; JIANG Chun-guo; LI Ji; XU Kai; XU Zuo-jun

    2011-01-01

    Background Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is the most frequent type of non-Hodgkin's lymphoma (NHL) that primarily involves the lungs. It represents a rare entity accounting for less than 1%of all NHLs and the clinical features have yet to be clearly elucidated.Methods The clinicopathological features and radiological data of 23 patients with pulmonary MALT lymphoma confirmed by biopsy in Peking Union Medical College Hospital from January 2001 to December 2010 were retrospectively analyzed.Results At diagnosis,there were 15 women and 8 men. The median age was 55.1 years (range,37-73 years). One patient had a history of primary Sjoren's syndrome,another patient had a history of systemic lupus erythematosus (SLE)and secondary Sjoren's syndrome. One patient had a history of previous hematological malignancy (lymphomatoid papulosis in complete remission). In addition,one patient had simultaneous gastric and pulmonary involvement and one patient had simultaneous parotid gland and pulmonary involvement. The other 21 patients had disease localized within the lungs at the initial diagnosis. Among them,10 patients were asymptomatic while two had non-specific pulmonary symptoms. There were six patients with fever,four patients had low grade fever and two patients had moderate-high fever.The most common manifestations were cough (n=10),expectoration (n=8),exertional dyspnea (n=8),fatigue (n=7),body weight loss (n=6) and crackles (n=6). Blood tests showed low to moderate anemia in six cases,elevated erythrocyte semimentation rate (ESR) in 10 cases and only one patient had elevated lactate dehydrogenase (LDH). High resolution computed tomography (HRCT) of the chest revealed bilateral disease in 13 patients,air space consolidation with or without air bronchogram in 15 patients,lung nodules in 15 patients,patchy opacities in eight patients,lung mass in three patients and pleural effusion in five patients. Flexible fiberoptic bronchoscopy showed

  15. Presence of a high-grade component in gastric mucosa-associated lymphoid tissue (MALT) lymphoma is not associated with an adverse prognosis.

    Science.gov (United States)

    Ang, Mei-Kim; Hee, Siew Wan; Quek, Richard; Yap, Swee Peng; Loong, Susan; Tan, Leonard; Tao, Miriam; Lim, Soon Thye

    2009-05-01

    Gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL) show a spectrum of disease characterized by varying proportions of low-grade and high-grade components. While the natural history and optimum treatment for low-grade gastric MALT lymphoma and DLBCL is well established, the prognosis and optimal treatment of patients with both low- and high-grade components is not well established. The purpose of our study was to evaluate the clinical characteristics, survival outcomes, and prognostic factors of patients with gastric MALT lymphoma and gastric DLBCL. A retrospective review of patients with gastric MALT lymphoma, gastric DLBCL, or MALT lymphoma with a high-grade component treated at our centers from 1994 to 2006 was performed. Patients were divided into three categories: "pure MALT lymphoma," "MALT lymphoma with high-grade component" (mixed), and "pure DLBCL." Seventy-six patients were included in our study-26 with pure MALT, 22 with MALT with high-grade component ("mixed"), and 28 with pure DLBCL. Pure MALT lymphoma and mixed lymphoma patients had similar clinical characteristics, whereas pure DLBCL patients had less favorable disease characteristics with significantly poorer performance status, higher number of extranodal sites of disease, higher stage, and larger proportion of bone marrow involvement and international prognostic index (IPI) scores compared with mixed lymphoma. The majority of mixed lymphoma (72.7%) and DLBCL patients (71.4%) were treated with chemotherapy. Of patients receiving chemotherapy, a higher proportion of mixed lymphoma and DLBCL patients received anthracycline-based combination chemotherapy regimens compared with MALT lymphoma (73% vs 71% vs 8%) whereas the proportion of mixed lymphoma and DLBCL patients was similar (p = 0.919). At a median follow-up of 37 months, the 5-year overall survival was 66.9%. The 5-year overall survival was 78% for MALT lymphoma, 84% for mixed lymphoma, and 45

  16. 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.

  17. 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

  18. Comparison of human memory CD8 T cell responses to adenoviral early and late proteins in peripheral blood and lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Amita Joshi

    Full Text Available Treatment of invasive adenovirus (Ad disease in hematopoietic stem cell transplant (SCT recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977 and late protein hexon (H-892 were compared in peripheral blood (PB and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16-24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients.

  19. Correlation of {sup 18}F-FDG PET/CT and Endoscopic Findings of Twin Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Stomach: Report of a Case

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Yong Whee; Choi, Jin Wook [SungAe Hospital, Seoul (Korea, Republic of)

    2008-02-15

    Mucosa-associated lymphoid tissue (MALT) type lymphoma arises from extranodal marginal zone B-cell. It is etiologically associated with Helicobacter pylori infection and, hence, can be cured by antibiotic treatment. MALT type lymphoma is the most common variety of gastric lymphoma that is rare in the stomach). The published data of clinical studies on the usefulness of 18F-FDG PET in the diagnosis of MALT type lymphoma varied according to authors. Thus, the result of Hoffmann et al. was discouraging whereas a high diagnostic accuracy was reported by Ambrosini et al. The latter group further went to suggest that higher 18F-FDG uptake in gastric MALT type lymphoma would positively relate to the aggressiveness of neoplasm. The clinical studies conducted by other groups on MALT lymphomas of the stomach, lung, orbit and parotid gland and the stomach, lung, parotid gland, skin, orbit, mandible, esophagus and uterus confirmed that 18F-FDG scan is valuable.

  20. 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.

  1. 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.

  2. 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.

  3. Interpretational Confounding or Confounded Interpretations of Causal Indicators?

    Science.gov (United States)

    Bainter, Sierra A.; Bollen, Kenneth A.

    2014-01-01

    In measurement theory, causal indicators are controversial and little understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning…

  4. Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

    Science.gov (United States)

    Carnegie, Nicole Bohme; Harada, Masataka; Hill, Jennifer L.

    2016-01-01

    A major obstacle to developing evidenced-based policy is the difficulty of implementing randomized experiments to answer all causal questions of interest. When using a nonexperimental study, it is critical to assess how much the results could be affected by unmeasured confounding. We present a set of graphical and numeric tools to explore the…

  5. 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.

  6. Immunohistochemical detection of SWC3, CD2, CD3, CD4 and CD8 antigens in paraformaldehyde fixed and paraffin embedded porcine lymphoid tissue

    DEFF Research Database (Denmark)

    Tingstedt, Jens Erik; Tornehave, Ditte; Lind, Peter

    2003-01-01

    with inherent poor tissue morphology, and are not readily adapted to formaldehyde fixed and paraffin embedded tissue with well preserved morphology. Seven well characterised monoclonal antibodies against porcine leukocyte antigens were tested on neutral buffered paraformaldehyde fixed and paraffin embedded...... for the detection of several major cell types of the porcine immune system in fixed tissue with optimal preservation of histological details.......Identification of the different cell types of the immune system is important for in situ studies on the pathogenesis of infectious diseases in various animals, including the pig. Unfortunately, many monoclonal anti-leukocyte antibodies are only useful for staining frozen tissue sections...

  7. Co-delivery of ccl19 gene enhances anti-caries DNA vaccine pCIA-P immunogenicity in mice by increasing dendritic cell migration to secondary lymphoid tissues

    Institute of Scientific and Technical Information of China (English)

    Yan-hong YAN; Sheng-cai QI; Ling-kai SU; Qing-an XU; Ming-wen FAN

    2013-01-01

    Aim:To investigate how co-delivery of the gene encoding C-C chemokine ligand-19 (CCL-19) affected the systemic immune responses to an anti-caries DNA vaccine pClA-P in mice.Methods:Plasmid encoding CCL19-GFP fusion protein (pCCL19/GFP) was constructed by inserting murine ccl19 gene into GFPexpressing vector pAcGFP1-N1.Chemotactic effect of the fusion protein on murine dendritic cells (DCs) was assessed in vitro and in vivo using transwell and flow cytometric analysis,respectively.BALB/c mice were administered anti-caries DNA vaccine pClA-P plus pCCL19/GFP (each 100 μg,im) or pClA-P alone.Serum level of anti-PAc IgG was assessed with ELISA.Splenocytes from the mice were stimulated with PAc protein for 48 h,and IFN-y and IL-4 production was measured with ELISA.The presence of pCCL19/GFP in spleen and draining lymph nodes was assessed using PCR.The expression of pCCL19/GFP protein in these tissues was analyzed under microscope and with flow cytometry.Results:The expression level of CCL19-GFP fusion protein was considerably increased 48 h after transfection of C0S-7 cells with pCCL19/GFP plasmids.The fusion protein showed potent chemotactic activity on DCs in vitro.The level of serum PAc-specific IgG was significantly increased from 4 to 14 weeks in the mice vaccinated with pCIA-P plus pCCL19/GFP.Compared to mice vaccinated with pCIA-P alone,the splenocytes from mice vaccinated with pClA-P plus pCCL19/GFP produced significantly higher level of IFN-Y,but IL-4 production had no significant change.Following intromuscular co-delivery,pCCL19/GFP plasmid and fusion protein were detected in the spleen and draining lymph nodes.Administration of CCL19 gene in mice markedly increased the number of mature DCs in secondary lymphoid tissues.Conclusion:CCL19 serves as an effective adjuvant for anti-caries DNA vaccine by inducing chemotactic migration of DCs to secondary lymphoid tissues.

  8. Confounding and Collapsibility in Causal Inference

    OpenAIRE

    Greenland, Sander; Robins, James M; Pearl, Judea

    1999-01-01

    Consideration of confounding is fundamental to the design and analysis of studies of causal effects. Yet, apart from confounding in experimental designs, the topic is given little or no discussion in most statistics texts. We here provide an overview of confounding and related concepts based on a counterfactual model for causation. Special attention is given to definitions of confounding, problems in control of confounding, the relation of confounding to exchangeability and ...

  9. Cell proliferation in lymphoid tissue and the seminiferous epithelium under continuous low level irradiation. Final report, 1 June 1967 to 15 July 1973

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J I

    1978-10-19

    The scientific scope and primary objectives of the research program concern investigations on (1) the kinetics of cellular proliferation and differentiation in the immunohematopoietic tissues and the reproductive tissues, and (2) the cellular response and cell population kinetics of these renewal tissues of the body under the stress of continuous low level irradiation. The directions and objectives of the research program have been continually broadened to include investigations on (1) the dynamics of the cellular and humoral immune responses, (2) interactions of host-defense mechanisms, (3) the cell proliferation kinetics in the ovary, and (4) cellular control mechanisms and human tumor cell kinetics.

  10. Genesis of lymphoid tissue and development of IgM-positive B cells in human fetal ileum%人胎回肠淋巴组织发生及IgM阳性B细胞的发育

    Institute of Scientific and Technical Information of China (English)

    胡蓉; 苏敏; 黄悦; 李红; 姜俸蓉; 许庭良

    2011-01-01

    目的 探讨人胎回肠淋巴组织的发生及IgM阳性B细胞在人胎回肠的分布、定位及发育. 方法 收集2003年1月至2005年12月贵阳市各医院妇产科因流产等终止妊娠的9~28周人胎回肠标本30例,男12例、女18例.采用HE染色观察人胎回肠淋巴组织发生,SABC法染色显示IgM阳性B细胞,并用BioMias29图像分析软件对免疫反应阳性细胞进行计数,有关数据作统计学分析.结果 胎龄9周时少量淋巴细胞分布于回肠上皮外的间充质内,其中部分细胞表达膜表面IgM.胎龄17周时固有层内淋巴组织局部聚集形成孤立淋巴小结,小结内含有较多IgM阳性B细胞.自24周起,人胎回肠可见典型的集合淋巴小结.IgM阳性B细胞主要分布于淋巴小结,少量弥散分布在固有层结缔组织或绒毛上皮内.细胞计数显示9~12周人胎回肠IgM阳性B细胞数量为(12.80±5.72)个,随胎龄增加至25~28周人胎回肠IgM阳性B细胞达(201.30±36.35)个,各胎龄组间比较差异显著(P<0.05).结论 24周人胎回肠壁淋巴组织结构基本发育成熟;人胎回肠具有潜在的IgM合成和释放能力,对胎儿肠道免疫功能的建立和健全起着重要作用.%Objective To study genesis of lymphoid tissue and distribution, localization and develop ment of lgM-positive B cells in human fetal ileum. Methods Human fetus specimens from terminated preg nancies, 12 males and 18 females with gestational ages of 9 -28 weeks, were collected from hospitals in Guiyang, China, between Jan. 2003 and Dec. 2005. All pregnant women were informed of the purpose of this study and the protocol was approved by the Ethics Committee of Guiyang Medical College. HE staining was adopted to observe the genesis of lymphoid tissue in human fetal ileum. IgM-positive B cells were detected by immunohistochemical SABC staining, and counted by BioMias 29 image analysis software. Relevant data were statistically analyzed. Results In the ilea of 9-week fetus

  11. 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.

  12. 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.

  13. Diagnosis and treatment of gastric non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue%胃黏膜相关性非霍奇金淋巴瘤的诊断和治疗

    Institute of Scientific and Technical Information of China (English)

    段彦红; 杨燕淑

    2008-01-01

    Objective To summarize the experience of diagnosis and treatment of gastric non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue.Methods Twenty-seven patients,proved by pathology,were included in the study.Results Among clinical presentations,the upper abdominal pain,intestinal bleeding,and weight loss were common.Only 1 case was diagnosed definitely from 18 cases with the examination of X-ray barium meal,84.6%(24 of 26 cases)were miss-diagnosed under gastroscopy.All cases underwent operation,among them 25 performed a radical operation.Twenty-four patients were followed up.Conclusion The multiple biopsy sampling from submueosal layer via gastroscope may improve diagnostic rate on gastric non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue.Operative removal of the tumor should be the first choice of treatment.Additional chemotherapy after the surgery increases survival rate.%目的 总结胃黏膜相关性非霍奇金淋巴瘤的诊治经验.方法 回顾性分析27例经病理证实的胃黏膜相关性非霍奇金淋巴瘤的诊治情况.结果 临床表现以卜腹痛、消化管出血、消瘦多见.18例行X线钡餐检查,仪1例确诊;26例行胃镜检查,有24例被误诊为胃癌或胃溃疡.所有病例均经手术治疗,其中根治性切除25例,随访24例.结论 重视胃黏膜相关性非霍奇金淋巴瘤的临床表现及X线检查特点,胃镜检查时多部位深取材可提高本病的诊断率,免疫组化检查有助于确诊.手术切除应为首选治疗,术后加用化疗以巩固疗效.

  14. Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy.

    Science.gov (United States)

    Zucca, Emanuele; Conconi, Annarita; Martinelli, Giovanni; Bouabdallah, Reda; Tucci, Alessandra; Vitolo, Umberto; Martelli, Maurizio; Pettengell, Ruth; Salles, Gilles; Sebban, Catherine; Guillermo, Armando Lopez; Pinotti, Graziella; Devizzi, Liliana; Morschhauser, Franck; Tilly, Hervé; Torri, Valter; Hohaus, Stefan; Ferreri, Andrés J M; Zachée, Pierre; Bosly, André; Haioun, Corinne; Stelitano, Caterina; Bellei, Monica; Ponzoni, Maurilio; Moreau, Anne; Jack, Andrew; Campo, Elias; Mazzucchelli, Luca; Cavalli, Franco; Johnson, Peter; Thieblemont, Catherine

    2017-06-10

    Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m(2)/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m(2) intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

  15. Primary renal mucosa-associated lymphoid tissue lymphoma,the result of chronic pyelonephritis?%肾脏黏膜相关淋巴瘤,是慢性肾孟肾炎的后果吗?

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective:To report 2 cases of primary renal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma), and observe the relations between this rare tumor of kidney and chronic pyelonephritis. Methods: 2renal MALT lymphomas were collected from referral consultation. Detailed clinical information were reviewed, morphological analysis based on the HE section, and immunohistochemistry were performed by CD20, CD79a, CDS, CD10, CD43, CD23,BCL10 and Cyclin D1 antibodies. Results: 2 female patients with age of 48 and 55, respectively, all had a history of chronic pyelonephritis. Under the B ultrasonic and CT scanning a bump in the kidney was found. Renal carcinoma suspected and hereby the whole nephrectomy performed. In the macroscopic, tumors were laid in the renal medulla, with dark red color and ill-defined boundary. In the microscopic, there were mixed lymphoid cells infiltrate which mainly consisted of small lymphocytes, centrocyte-like cells, lymphoplasmacytoid and plasma cells, reactive follicles and lymphoepithelial lesions also could be seen in the lesion, but follicles colonization was rare. In fact, except changes of lymphoma, basic renal disease also could be seen. Most glomeruli were atrophic, some glomeruli were hyperplastic and hypertrophic. Tubules were dilated or contacted, many dilated tubules contained pink-color glassy-appearing casts that suggest the appearance of thyroid tissue.As a result, those 2 cases showed juxtaposed changes of lymphoma and pyelonephritis. Immunohistochemistry showed that tumor cells were CD20 and CD79a positive, CD43 was weak positive, but CD5, CD10, CD23, BCL10 and Cyclin D1 were all negative. Conclusion: Primary renal MALT lymphoma was very rare disease. According to the clinical manifestation, it's hard to differentiate from renal cell carcinoma. But the morphological features were consistent with the classic MALT lymphomas in other sites. Immunophenotypic profiles were helpful for diagnosis. Based

  16. 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.

  17. Detection of infectious bursal disease virus in various lymphoid tissues of experimentally infected specific pathogen free chickens by different reverse transcription polymerase chain reaction assays

    DEFF Research Database (Denmark)

    Kabell, Susanne; Handberg, Kurt; Kusk, Mette;

    2005-01-01

    transcription polymerase chain reaction (RT-PCR) assays, including two recently developed strain-specific assays, were employed for detection of ribonucleic acid (RNA) from three different IBDV strains in bursa tissue samples from experimentally infected specific pathogen free chickens. The virus strains...

  18. Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study

    Science.gov (United States)

    Scagnolari, Carolina; Corano Scheri, Giuseppe; Selvaggi, Carla; Schietroma, Ivan; Najafi Fard, Saeid; Mastrangelo, Andrea; Giustini, Noemi; Serafino, Sara; Pinacchio, Claudia; Pavone, Paolo; Fanello, Gianfranco; Ceccarelli, Giancarlo; Vullo, Vincenzo; d’Ettorre, Gabriella

    2016-01-01

    Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients’ quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In order to evaluate this issue, we measured the levels of neopterin in CSF, and the expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1-infected patients on effective combined antiretroviral therapy (cART), at baseline and after six months of probiotic dietary management. We found a significant reduction of neopterin and IDO mRNA levels after the supplementation with probiotic. Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial. PMID:27689995

  19. Regulation of carbohydrate metabolism in lymphoid tissue. Nature of the endogenous substrates and their contribution to the respiratory fuel of the sliced rat spleen in vitro.

    Science.gov (United States)

    Suter, D; Weidemann, M J

    1976-04-15

    1. Tissue glycogen contributes, maximally, only 10% of the respiratory fuel of the rat spleen slice in the absence of an added carbon source, and makes no significant contribution when glucose (3mM) is added. 2. The reserves of fatty acid in the form of triglyceride (35.5mumol of fatty acid/g dry wt. of tissue) fall by approx. 25% after incubation of spleen slices with or without added glucose for 2h, and , on this basis, account for 32% of the oxidative fuel. 3. In contrast, the total oxidative contribution of fatty acid reserves to the respiratory fuel, determined on the basis of inhibiton of respiration by 2-bromostearate, is 42-52%. This range includes tissue from both starved and well-fed animals and is not significantly altered by the presence of added glycose (3mM). 4. Large quantities of NH3 (31-35mumol//h per g dry wt. of tissue) are produced by spleen slices incubated in the absence of added substrates, and this value is suppressed by approx. 50% on incubation with glucose (3mM). Adenine nucleotide breakdown can account for only 17% of the total ammonia produced. 5. Individual free amino acid concentrations in spleen were determined, both in vivo and in slices before and after 60 min of incubation. Although the total free amino acid pool size increases by 45% during incubation, owing to protein breakdown, the tissue concentrations of aspartate, glutamate, glutamine and alanine do not increase. It is suggested that these amino acids areoxidized in a net sense to CO2 and water with the liberation of free NH3 via transamination reactions, glutaminase, the purine nucleotide cycle and the tricarboxylic acid cycle. 6. It is concluded that the normal endogenous metabolism of sliced rat spleen (43-52% due to lipids, 30% due to amino acids and 10% due to glycogen) is modified by added glycose only to the extent that glycogen oxidation and 50% of the contribtion made by ino acids are suppressed; endogenous lipid metabolism is unaffected.

  20. 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

  1. 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.

  2. 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.

  3. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Holmskov, U.; Aalbæk, B.;

    2005-01-01

    Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic...... among pSP-D, pathogens, phagocytic cells and dendritic cells. Lung tissue was collected from experimental and natural bronchopneumonias caused by Actinobacillus pleuropneumoniae or Staphylococcus aureus, and from embolic and diffuse interstitial pneumonia, caused by Staph. aureus or Arcanobacterium......SP-D through the specialized M cells overlying (BALT). In conclusion, we have shown that pSP-D expression in the lung surfactant is induced by bacterial infection by an aerogenous route rather than by a haematogenous route, and that the protein interacts specifically with alveolar macrophages...

  4. Impact of invA-PCR and culture detection methods on occurrence and survival of salmonella in the flesh, internal organs and lymphoid tissues of experimentally infected pigs.

    Science.gov (United States)

    Arnold, T; Scholz, H C; Marg, H; Rösler, U; Hensel, A

    2004-12-01

    This study evaluated the suitability of invA gene amplification by PCR as an effective means of detecting Salmonella species in pigs experimentally infected with S. Typhimurium DT104. A controlled infection study using 24 pigs was performed in order to compare efficacy, precision and detection rates of the invA-based PCR method originally described by Rahn, K. De Grandis, S.A., Clarke, R.C., McEwan, S.A., Galan, J.E., Ginocchio, C., Curtiss, R. 3rd, C.L. Gyles, (Mol. Cell. Probes 1992; 6: 271-279) as a new in-house invA-based PCR method for the specific detection of Salmonella spp. in pork and different tissue samples of slaughter pigs. Finally, PCR results were compared with culture detection rates obtained by isolation procedures following the ISO 6579:2000, the 'gold standard'. After slaughtering, 14 different tissue samples of each pig were investigated to verify the usefulness of the two invA-based PCR methods in different matrices of slaughter pigs. The results demonstrate that the application of the widely used invA-based primer pair (139 + 141) may result in questionable products if samples gained from selective enrichment in the Rappaport-Vassiliadis medium were investigated. These questionable products can lead to false-positive results, if no additional hybridization procedure is attached or if unspecialized persons use this method in routine laboratory practice. The newly developed in-house PCR method used is based on the 3'-prime region of invA, especially designed and harmonized for the detection of Salmonella in different matrices of slaughtered pigs after bacterial enriched broth culture. In this study, this PCR revealed no questionable products and, furthermore, the specificity of the amplificate could be tested by means of the restriction enzyme NdeI. In comparison with the culture detection procedure, the new PCR method has a sensitivity of 100% and a specificity of 96%. Thus, this method might be used as a meaningful tool in eliminating

  5. Effect of a cocoa diet on the small intestine and gut-associated lymphoid tissue composition in an oral sensitization model in rats.

    Science.gov (United States)

    Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Untersmayr, Eva; Castell, Margarida

    2017-04-01

    Previous studies have attributed to the cocoa powder the capacity to attenuate the immune response in a rat oral sensitization model. To gain a better understanding of cocoa-induced mechanisms at small intestinal level, 3-week-old female Lewis rats were fed either a standard diet or a diet containing 10% cocoa for 4 weeks with or without concomitant oral sensitization with ovalbumin (OVA). Thereafter, we evaluated the lymphocyte composition of the Peyer's patches (PPL), small intestine epithelium (IEL) and lamina propria (LPL). Likewise, gene expression of several immune molecules was quantified in the small intestine. Moreover, histological samples were used to evaluate the proportion of goblet cells, IgA+ cells and granzyme+cells as well. In cocoa-fed animals, we identified a five-time reduction in the percentage of IgA+ cells in intestinal tissue together with a decreased proportion of TLR4+ IEL. Analyzing the lymphocyte composition, almost a double proportion of TCRγδ+cells and an increase of NK cell percentage in PPL and IEL were found. In addition, a rise in CD25+, CD103+ and CD62L- cell proportions was observed in CD4+ PPL from cocoa-fed animals, along with a decrease in gene expression of CD11b, CD11c and IL-10. These results suggest that changes in PPL and IEL composition and in the gene expression induced by the cocoa diet could be involved, among other mechanisms, on its tolerogenic effect.

  6. 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

  7. Pooling of Confounders Did Not Induce Residual Confounding in Influenza Vaccination Studies

    NARCIS (Netherlands)

    Groenwold, Rolf H. H.; Hak, Eelko; Hoes, Arno W.

    2009-01-01

    PURPOSE: In observational studies on influenza vaccine effectiveness, confounding variables such as individual chronic diseases often are pooled before inclusion into a multivariable regression model. It has been suggested, however, that the pooling of confounders induces residual confounding, altho

  8. Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Bei; Dou, Yannong; Wang, Ting; Yu, Juntao; Wu, Xin; Lu, Qian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China); Chou, Guixin; Wang, Zhengtao [Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Kong, Lingyi [Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Dai, Yue, E-mail: yuedaicpu@hotmail.com [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China); Xia, Yufeng, E-mail: yfxiacpu@126.com [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China)

    2015-01-01

    Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic–pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3{sup +} cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR. - Highlights: • Norisoboldine, administered orally, markedly attenuates the clinical signs of CIA. • Norisoboldine regulates the balance of Th17/Treg cells in the intestinal lymph node. • Norisoboldine induces the migration of Treg cells from the gut to joint.

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

    Science.gov (United States)

    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.

  10. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    Science.gov (United States)

    Pérez de Diego, Rebeca; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Ferreira Cerdán, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Marine oils: Complex, confusing, confounded?

    Directory of Open Access Journals (Sweden)

    Benjamin B. Albert

    2016-09-01

    Full Text Available Marine oils gained prominence following the report that Greenland Inuits who consumed a high-fat diet rich in long-chain n-3 polyunsaturated fatty acids (PUFAs also had low rates of cardiovascular disease. Marine n-3 PUFAs have since become a billion dollar industry, which will continue to grow based on current trends. However, recent systematic reviews question the health benefits of marine oil supplements, particularly in the prevention of cardiovascular disease. Marine oils constitute an extremely complex dietary intervention for a number of reasons: i the many chemical compounds they contain; ii the many biological processes affected by n-3 PUFAs; iii their tendency to deteriorate and form potentially toxic primary and secondary oxidation products; and iv inaccuracy in the labelling of consumer products. These complexities may confound the clinical literature, limiting the ability to make substantive conclusions for some key health outcomes. Thus, there is a pressing need for clinical trials using marine oils whose composition has been independently verified and demonstrated to be minimally oxidised. Without such data, it is premature to conclude that n-3 PUFA rich supplements are ineffective.

  12. Toxicity to nasal-associated lymphoid tissue

    NARCIS (Netherlands)

    Kuper, C.F.; Arts, J.H.E.; Feron, V.J.

    2003-01-01

    The mucosal membranes form a weak mechanical barrier, but they are provided with an extensive specific and non-specific defence system. Antigenic stimulation of the mucosal immune system of the oronasal passages induces specific, local immune responses, and activates immune components of mucosae els

  13. 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

  14. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules.

    Science.gov (United States)

    Stein, J V; Rot, A; Luo, Y; Narasimhaswamy, M; Nakano, H; Gunn, M D; Matsuzawa, A; Quackenbush, E J; Dorf, M E; von Andrian, U H

    2000-01-03

    T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function-associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a Galpha(i)-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T(GFP) cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling T(GFP) cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T(GFP) cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T(GFP) cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, T(GFP) cells rolled but did not arrest in plt/plt HEVs. When TCA-4 was injected intracutaneously into plt/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1-mediated T(GFP) cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs.

  15. A Case of Testicular Primary Mucosa-associated Lymphoid Tissue Lymphoma%睾丸黏膜相关性淋巴组织型淋巴瘤1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    杨丽

    2014-01-01

    目的:报道1例睾丸原发性黏膜相关性淋巴组织淋巴瘤(B细胞型),并分析其病理特征及鉴别诊断。方法:对MALT淋巴瘤进行HE及免疫组化染色,结合文献对其进行分析。结果:瘤细胞在曲细精管之间浸润,严重处可使曲细精管被破坏或受挤压而萎缩,细胞大,细胞之间非粘着性生长,有大而不规则的核。免疫组化标记显示瘤细胞CD20和Vim(+),HCG、PLAP、CD45 RO、CK19均为(~)。结论:MALT淋巴瘤是一种少见的恶性肿瘤,形态学上应当与精原细胞瘤、慢性睾丸炎、胚胎性横纹肌肉瘤相鉴别,免疫组化标记对于鉴别诊断很有帮助。%Objective:Report a case of testicular primary mucosa -associated lymphoid tissue lymphoma ( B cell type) , and to analyze the pathological features and differential diagnosis .Methods:The MALT lymphoma were analyzed by HE and immunohistochemical stai-ning, with review of the literature on the .Results:Tumor cell infiltration between the seminiferous tubules , serious can cause seminiferous tubules were damaged or crushed and atrophy , cell growth , cell non-adhesive , with large and irregular nucleus .Immunohistochemically , tumor cells CD20 and Vim (+), HCG, PLAP, CD45RO, CK19 were (-).Conclusion:MALT lymphoma is a rare tumor, morphology should differentiate with seminoma , chronic orchitis , embryonal rhabdomyosarcoma , immunohistochemistry is helpful for the differential diagnosis.

  16. Characteristics of histological location of bursin in sacculus rotundus and gut-associated lymphoid tissues of rabbits%法式囊三肽囊素(bursin)在兔圆小囊、肠相关淋巴组织(蚓突)中免疫组化定位特征研究

    Institute of Scientific and Technical Information of China (English)

    吴石金; 谌南辉

    2007-01-01

    The distribution of bursin in sacculus rotundus and gut-associated lymphoid tissues was investigated in rabbit by immuno-histochemical staining method with anti-bursin monoclonal antibody (McAb)2F9-4. The results indicated that the appearance of the bursin-containing cells coincided with the morphodifferentiation and growth process in rabbit. Bursin immunized cells not only distributed in dome epithelium and mucosal epithelium, but also in follicular germinal center, dome, T-cell area, goblet cell, inter-epithelial lymphocyte and cap-zone of sacculus rotundus. This founding suggested that bursincontaining cells in sacculus rotundus might play an important role in intestinal mucosal immunity.

  17. Self-controlled designs to control confounding

    NARCIS (Netherlands)

    Pouwels, Koen

    2015-01-01

    The best available evidence for decision-making on interventions will often come from observational studies. Given the vulnerability of observational studies to confounding, complete and transparent reporting on confounding is necessary to enable readers to assess the validity of study findings. In

  18. Identifying confounders using additive noise models

    CERN Document Server

    Janzing, Dominik; Mooij, Joris; Schoelkopf, Bernhard

    2012-01-01

    We propose a method for inferring the existence of a latent common cause ('confounder') of two observed random variables. The method assumes that the two effects of the confounder are (possibly nonlinear) functions of the confounder plus independent, additive noise. We discuss under which conditions the model is identifiable (up to an arbitrary reparameterization of the confounder) from the joint distribution of the effects. We state and prove a theoretical result that provides evidence for the conjecture that the model is generically identifiable under suitable technical conditions. In addition, we propose a practical method to estimate the confounder from a finite i.i.d. sample of the effects and illustrate that the method works well on both simulated and real-world data.

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

    Science.gov (United States)

    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. Confounding and bias in the attributable fraction.

    Science.gov (United States)

    Darrow, Lyndsey A; Steenland, N Kyle

    2011-01-01

    Inappropriate methods are frequently used to calculate the population attributable fraction (AF) for a given exposure of interest. This commonly occurs when authors use adjusted relative risks (RRs) reported in the literature (the "source" data), without access to the original data. In this analysis, we examine the relationship between the direction and magnitude of confounding in the source data and resulting bias in the attributable fraction when incorrect methods are used. We assess confounding by the confounding risk ratio, which is the ratio of the crude RR to the adjusted RR. We assess bias in the AF by the ratio of the incorrectly calculated AF to the correctly calculated AF. Using generated data, we examine the relationship between confounding and AF bias under various scenarios of population prevalence of exposure and strength of the exposure-disease association. For confounding risk ratios greater than 1.0 (ie, crude RR >adjusted RR), the AF is underestimated; for confounding risk ratios less than 1.0 (ie, crude RR confounding increases, and is dependent on the prevalence of exposure in the total population, with bias greatest at the lowest prevalence of exposure. Bias in the AF is also higher when the exposure-disease association is weaker. Results of these analyses can assist interpretation of incorrectly calculated attributable fraction estimates commonly reported in the epidemiologic literature.

  1. 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.

  2. Assessing the impact of unmeasured confounding for binary outcomes using confounding functions.

    Science.gov (United States)

    Kasza, Jessica; Wolfe, Rory; Schuster, Tibor

    2017-03-03

    A critical assumption of causal inference is that of no unmeasured confounding: for estimated exposure effects to have valid causal interpretations, a sufficient set of predictors of exposure and outcome must be adequately measured and correctly included in the respective inference model(s). In an observational study setting, this assumption will often be unsatisfied, and the potential impact of unmeasured confounding on effect estimates should be investigated. The confounding function approach allows the impact of unmeasured confounding on estimates to be assessed, where unmeasured confounding may be due to unmeasured confounders and/or biases such as collider bias or information bias. Although this approach is easy to implement and pertains to the sum of all bias, its use has not been widespread, and discussion has typically been limited to continuous outcomes. In this paper, we consider confounding functions for use with binary outcomes and illustrate the approach with an example. We note that confounding function choice encodes assumptions about effect modification: some choices encode the belief that the true causal effect differs across exposure groups, whereas others imply that any difference between the true causal parameter and the estimate is entirely due to imbalanced risks between exposure groups. The confounding function approach is a useful method for assessing the impact of unmeasured confounding, in particular when alternative approaches, e.g. external adjustment or instrumental variable approaches, cannot be applied. We provide Stata and R code for the implementation of this approach when the causal estimand of interest is an odds or risk ratio.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 胃黏膜相关淋巴样组织淋巴瘤42例临床分析%Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: a Clinical Analysis of 42 Patients

    Institute of Scientific and Technical Information of China (English)

    卓长华; 应敏刚; 梁寒; 臧卫东; 陈路川

    2011-01-01

    Objective: Primary gastric lymphomas account for 4.6% of non-Hodgkin lymphomas ( NHL ).Over the past several years, significant attention has been paid to the gastric mucosa-associated lymphoid tissues ( MALT ), a low-grade gastric B cell lymphoma, due to a close correlation between the incidence of MALT and Helicobacter pylori infection.The aim of the present study was to discuss the clinical features, pathological diagnosis, and therapeutic regimen of gastric MALT lymphoma.Methods: Clinicopathologic features and data of clinical stages of 42 patients with gastric MALT lymphoma, who were admitted to Tianjin Medical University Cancer Institute and Hospital between July 1990 and May 2008, were retrospectively analyzed.The cases were divided according to the treatment administered, namely, 7 patients by H.pylori eradication, 9 by surgery, 20 by surgery plus H.pylori eradication, and 6 by surgery plus chemotherapy or radiotherapy.The Kaplan-Meier method was used to analyze the survival rates, and the Log rank test was performed to assess the statistical significance among the groups.Results: All patients received gastroscopy and biopsy.However, only 11 of the 42 patients ( 26.2% ) were pathologically confirmed.H.pylori strain was positive in 24 of 34 patients ( 70.6% ).The results of the immunophenotypic analysis confirmed these tumors to be B-cell lymphoma.Based on the Cotswolds modification of theAnnArbor Staging System, 17 of the cases were at stage IE2, 16 at stage ⅡE1, 6 at stage ⅡE2, two at stage ⅡE, and one at stage Ⅳ, respectively.Survival analysis indicated that the 5-year survival rates were 100%, 83.7%, 82.4%, and 43.0%, respectively, in the 4 groups ( P = 0.027 ).Conclusion: There are no remarkable characteristics in the clinical manifestation and auxiliary examination of the gastric MALT lymphoma.Thus, very few patients received surgery at the initial treatment, choosing either Hp eradication or radiotherapy instead.Hp eradication

  7. 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.

  8. Confounding and control of confounding in nonexperimental studies of medications in patients with CKD.

    Science.gov (United States)

    Bradbury, Brian D; Gilbertson, David T; Brookhart, M Alan; Kilpatrick, Ryan D

    2012-01-01

    Confounding is an important source of bias in nonexperimental studies, arising when the effect of an exposure on the occurrence of an outcome is distorted by the effect of some other factor. In nonexperimental studies of patients with CKD or who are on chronic dialysis, confounding is a significant concern owing to the high burden of comorbid disease, extent of required clinical management, and high frequency of adverse clinical events in this patient population. Confounding can be addressed in both the design stage (restriction, accurate measurement of confounders) and analysis stage (stratification, multivariable adjustment, propensity scores, marginal structural models, instrumental variable) of a study. Time-dependent confounding and confounding by indication are 2 special cases of confounding that can arise in studies of treatment effects and may require more sophisticated analytic techniques to adequately address. The availability and expanded use of large health care databases have ensured greater precision and have now placed the focus on validity. Addressing the major threats to validity, such as confounding, should be a first-order concern.

  9. 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.

  10. 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.

  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. 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...

  13. 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.

  14. Confounding in publications of observational intervention studies

    NARCIS (Netherlands)

    Groenwold, Rolf H. H.; Hoes, Arno W.; Hak, Eelko

    2007-01-01

    We conducted a systematic literature search in Medline to assess the proportion of observational intervention studies appreciating confounding bias in peer-reviewed medical literature from 1985 through 2005. This study shows only 9% of all papers on observational intervention studies published in pe

  15. Modeling confounding by half-sibling regression

    DEFF Research Database (Denmark)

    Schölkopf, Bernhard; Hogg, David W; Wang, Dun

    2016-01-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both...

  16. Prognostic value of t(11; 18) (q21; q21) for gastric mucosa-associated lymphoid tissue lymphoma%t(11;18)染色体易位对于胃黏膜相关淋巴组织淋巴瘤的预后价值

    Institute of Scientific and Technical Information of China (English)

    陈涛; 岑岭; 肖溶; 杨建和; 姜乃可; 卢绪章; 章艳; 陆静涛

    2012-01-01

    Objective To investigate the prognostic value of t(11;18)(q21;q21)in gastric mucosa-associated lymphoid tissue lymphoma.Methods A cohort of thirty-six gastric mucosa-associated lymphoid tissue lymphoma patients who were pathologically identify diagnosis from January 1994 to June 2004 were followed up retrospectively and studied using fluorescence in situ hybridization(FISH) technique to detect t(11;18) (q21;q21) chromosomal translocation on preservative paraffin specimen.Results Among thirty-six patients,fifteen (41.67%) were positive for t(11;18) (q21;q21).All but one were followed up to March 2010,general median survival time (MST) was 87 months.The MST were 43 and 130 months for t(11;H8) positive and negative patients,respectively.The MST between these two groups was notably different (x2 =29.57,P<0.01).Conclusion t(11;18) (q21;q21) is important prognostic factor for gastric mucosa-associated lymphoid tissue lymphoma.%目的 探讨t(11;18)(q21;q21)染色体易位对于胃黏膜相关淋巴组织(mucosal associated lymphoid tissue,MALT)淋巴瘤预后意义.方法 采用回顾性方法对1994年1月至2004年6月间,经术后病理明确诊断的36例MALT淋巴瘤患者进行随访,同时采用间期荧光原位杂交技术检测患者保存的石蜡手术标本有无t(11;18)(q21;q21)染色体易位.结果 36例患者中15例检出t(11;18)(q21;q21)染色体易位,阳性率为41.67%;35例随访至2010年3月,总的中位生存期87个月,伴有t(11;18)(q21;q21)染色体易位者的中位生存期为43个月,无t(11;18)(q21;q21)染色体易位者的中位生存期为130个月,两组之间差异有统计学意义(x2 =29.57,P<0.01).结论 t(11;18)(q21;q21)染色体易位是MALT淋巴瘤的重要预后因素.

  17. 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.

  18. 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.

  19. 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.

  20. [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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 原发性胃淋巴瘤凋亡抑制蛋白2-黏膜相关淋巴瘤转位基因1融合基因检测的意义%The clinical value of apoptosis protein 2-mucosa associated lymphoid tissue lymphoma translocation gene 1 fusion gene detection in tissue of primary gastric lymphoma

    Institute of Scientific and Technical Information of China (English)

    许国强; 陈妙辉; 陈洪潭; 单国栋; 胡凤玲; 杨铭

    2011-01-01

    Objective To explore the feasibility of inhibitor of apoptosis protein 2-mucosa associated lymphoid tissue lymphoma translocation gene 1 (API2-MALT1) fusion gene detection in endoscopic biopsy tissue of primary gastric lymphoma (PGL), and to study the expression of this fusion gene in PGL and its clinical values in diagnosis and treatment of PGL.Methods A total of 32 suspicious PGL patients underwent endoscopic ultrasonography (EUS) examination and mucosal biopsy.The biopsy specimens were conducted histopathology examination, immunohistochemistry detection and real time RT-PCR for API2-MALT1 fusion gene expression.The expression of API2MALT1 fusion gene in clearly diagnosed PGL and its relation with PGL diagnosis, classification and treatment were analyzed and summarized.Results A total of 14 cases of 32 suspicious PGL patients were diagnosed as PGL by histopathology and immunohistochemistry examination, which including 11 cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and 3 cases of gastric diffuse large B-cell lymphoma (DLBCL).There were 5 API2-MALT1 fusion gene positive cases, which were all MALT lymphoma, about 5 out of total 11 MALT lymphoma patients.API2-MALT1 fusion gene expression was negative in all 3 gastric DLBCL cases.The depth of lesion invasion and lymph nodes metastasis were more severe in API2-MALT1 fusion gene negative group than those of positive group.There were 2 of 5 API2-MALT1 fusion gene positive cases were Hp positive, and 5 of 9 negative cases were Hp positive.The anti-Hp therapy in 5 API2-MALT1 fusion gene positive cases was ineffective,however, chemotherapy was effective.In negative group, 2 of 5 Hp positive cases was complete remission and 4 Hp negative cases were ineffective with anti-Hp therapy.Concltsions API2-MALT1 fusion gene is common genetic abnormality in gastric MALT lymphoma.The detection of this fusion gene expression in endoscopic biopsy specimen by real time RT-PCR is clinically practical, and the

  3. 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.

  4. Total lymphoid irradiation and discordant cardiac xenografts

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. A typology of four notions of confounding in epidemiology.

    Science.gov (United States)

    Suzuki, Etsuji; Mitsuhashi, Toshiharu; Tsuda, Toshihide; Yamamoto, Eiji

    2017-02-01

    Confounding is a major concern in epidemiology. Despite its significance, the different notions of confounding have not been fully appreciated in the literature, leading to confusion of causal concepts in epidemiology. In this article, we aim to highlight the importance of differentiating between the subtly different notions of confounding from the perspective of counterfactual reasoning. By using a simple example, we illustrate the significance of considering the distribution of response types to distinguish causation from association, highlighting that confounding depends not only on the population chosen as the target of inference, but also on the notions of confounding in distribution and confounding in measure. This point has been relatively underappreciated, partly because some literature on the concept of confounding has only used the exposed and unexposed groups as the target populations, while it would be helpful to use the total population as the target population. Moreover, to clarify a further distinction between confounding "in expectation" and "realized" confounding, we illustrate the usefulness of examining the distribution of exposure status in the target population. To grasp the explicit distinction between confounding in expectation and realized confounding, we need to understand the mechanism that generates exposure events, not the product of that mechanism. Finally, we graphically illustrate this point, highlighting the usefulness of directed acyclic graphs in examining the presence of confounding in distribution, in the notion of confounding in expectation.

  6. Noisy-OR Models with Latent Confounding

    CERN Document Server

    Hyttinen, Antti; Hoyer, Patrik O

    2012-01-01

    Given a set of experiments in which varying subsets of observed variables are subject to intervention, we consider the problem of identifiability of causal models exhibiting latent confounding. While identifiability is trivial when each experiment intervenes on a large number of variables, the situation is more complicated when only one or a few variables are subject to intervention per experiment. For linear causal models with latent variables Hyttinen et al. (2010) gave precise conditions for when such data are sufficient to identify the full model. While their result cannot be extended to discrete-valued variables with arbitrary cause-effect relationships, we show that a similar result can be obtained for the class of causal models whose conditional probability distributions are restricted to a `noisy-OR' parameterization. We further show that identification is preserved under an extension of the model that allows for negative influences, and present learning algorithms that we test for accuracy, scalabili...

  7. 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.

  8. Bias Analysis for Uncontrolled Confounding in the Health Sciences.

    Science.gov (United States)

    Arah, Onyebuchi A

    2017-03-20

    Uncontrolled confounding due to unmeasured confounders biases causal inference in health science studies using observational and imperfect experimental designs. The adoption of methods for analysis of bias due to uncontrolled confounding has been slow, despite the increasing availability of such methods. Bias analysis for such uncontrolled confounding is most useful in big data studies and systematic reviews to gauge the extent to which extraneous preexposure variables that affect the exposure and the outcome can explain some or all of the reported exposure-outcome associations. We review methods that can be applied during or after data analysis to adjust for uncontrolled confounding for different outcomes, confounders, and study settings. We discuss relevant bias formulas and how to obtain the required information for applying them. Finally, we develop a new intuitive generalized bias analysis framework for simulating and adjusting for the amount of uncontrolled confounding due to not measuring and adjusting for one or more confounders.

  9. 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.

  10. 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.

  11. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  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. Rhesus monkeys exposed intravaginally to Simian Immunodeficiency Virus have a characteristic pattern of cytokine, chemokine and Foxp3 expression in the genital tract, intestine and lymphoid tissues despite vastly different levels of viral replication and

    Institute of Scientific and Technical Information of China (English)

    Z.M.; Ma; K.; Abel; T.; Rourke; Y.; Wang; M.B.; McChesney; C.J.

    2005-01-01

    Intravaginal inoculation with pathogenic SIVproduces atypical systemic infectionin most exposed animals andthe rema-ining animals are plasma vRNAnegative and anti-SIVantibody negative.Thusthe animalsfitthe categoryof exposed-un-infected monkeys.However,SIVRNAor DNAcan be detectedinthe tissues of many of these animals,indicatingthatatypical infections occur withconsiderablefrequency afterintravaginal SIVexposure.We pursued anindirect approachtoconfirmthat the exposed-uninfected animals were truly uninfected ...

  16. 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.

  17. Addressing the path-length-dependency confound in white matter tract segmentation

    DEFF Research Database (Denmark)

    Liptrot, Matthew George; Sidaros, Karam; Dyrby, Tim B.

    2014-01-01

    We derive the Iterative Confidence Enhancement of Tractography (ICE-T) framework to address the problem of path-length dependency (PLD), the streamline dispersivity confound inherent to probabilistic tractography methods. We show that PLD can arise as a non-linear effect, compounded by tissue...

  18. Methodological issues of confounding in analytical epidemiologic studies.

    Science.gov (United States)

    Hajian Tilaki, Karimollah

    2012-01-01

    Confounding can be thought of as mixing the effect of exposure on the risk of disease with a third factor which distorts the measure of association such as risk ratio or odds ratio. This bias arises because of complex functional relationship of confounder with both exposure and disease (outcome). In this article, we provided a conceptual framework review of confounding issues in epidemiologic studies, in particular in observational studies and nonrandomized experimental studies. We have shown in 2 by 2 tables with analytical examples how the index of association will be distorted when confounding is present. The criteria, source of confounding and several points in confounding issues have been addressed. The advantages and disadvantages of several strategies for control of confounding have been discussed.

  19. Confounding Effect in Clinical Research of Otolaryngology and Its Control.

    Science.gov (United States)

    Yu, Yong-qiang; Huang, Dong-yan; Armijo Olivo, Susan; Yang, Huai-an; Bambanini, Yagesh; Sonnenberg, Lyn; Clark, Brenda; Constantinescu, Gabriela; Qian Yu, Jason; Zhang, Ming

    2015-06-01

    Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.

  20. Confounding Effect in Clinical Research of Otolaryngology and Its Control

    Institute of Scientific and Technical Information of China (English)

    Yong-qiang Yu; Ming Zhang; Dong-yan Huang; Susan Armijo Olivo; Huai-an Yang; Yagesh Bambanini; Lyn Sonnenberg; renda Clark; Gabriela Constantinescu; Jason Qian Yu

    2015-01-01

    Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research’s conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research’s design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research’s design in which appropriate methods have been applied to prevent this effect. They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.

  1. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1+ DCs in mouse and human and distinguishes them from Langerhans cells

    Science.gov (United States)

    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-01-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1+ DCs, and between mouse and human Langerhans cells. PMID:26966045

  2. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.

    Science.gov (United States)

    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-05-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Confounders of auscultatory blood pressure measurement.

    Science.gov (United States)

    Baker, R H; Ende, J

    1995-04-01

    The appropriate use of any test requires the clinician to appreciate that test's limitations. By recognizing the potential confounders of the auscultatory assessment of blood pressure, the clinician minimizes the likelihood of enacting therapeutic decisions based on inaccurate data. When approaching the treatment of a hypertensive patient, several points should be kept in mind. First, the measurement of persistent and severe hypertension in a patient receiving treatment who describes symptoms of orthostatic hypotension with apparently adequate standing blood pressure or who lacks corroborating retinal, echocardiographic, or electrocardiographic signs of hypertension should raise the concern of pseudohypertension or a white-coat response. Similarly, when one finds a normal or near-normal systolic blood pressure in a patient with a clinical picture consistent with severe hypertension, one should make a directed effort to look for an unrecognized auscultatory gap. Second, marked discrepancies in measurements as obtained by different operators or in different settings should raise concern of the white-coat response or methodologic errors by one operator, such as undercuffing, excessive pressure on the head of the stethoscope, rapid deflation of the cuff, or use of different arms. In treating hypertension in even the minimally obese patient, a special point must be made that an adequate size cuff be used for all blood pressure determinations. Third, when blood pressure is determined with the patient in any but the satndardized back-and-arm-supported seated position described above, the clinician should acknowledge the possibility that the position may alter the patient's classification. Fourth, the diagnosis and management of hypertension requires multiple measurements of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. 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.

  5. 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.

  6. 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

  7. Confounding in longitudinal studies in addiction treatment research.

    Science.gov (United States)

    Pierce, Matthias; Dunn, Graham; Millar, Tim

    2017-05-04

    Background: The effectiveness of treatment for people with substance use disorders is usually examined using longitudinal cohorts. In these studies, treatment is often considered as a time-varying exposure. The aim of this commentary is to examine confounding in this context, when the confounding variable is time-invariant and when it is time-varying. Method: Types of confounding are described with examples and illustrated using path diagrams. Simulations are used to demonstrate the direction of confounding bias and the extent that it is accounted for using standard regression adjustment techniques. Results: When the confounding variable is time invariant or time varying and not influenced by prior treatment, then standard adjustment techniques are adequate to control for confounding bias, provided that in the latter scenario the time-varying form of the variable is used. When the confounder is time varying and affected by prior treatment status (i.e. it is a mediator of treatment), then standard methods of adjustment result in inconsistency. Conclusions: In longitudinal cohorts where treatment exposure is time varying, confounding is an issue which should be considered, even if treatment exposure is initially randomized. In these studies, standard methods of adjustment may result be inadequate, even when all confounders have been identified. This occurs when the confounder is also a mediator of treatment. This is a likely scenario in many studies in addiction.

  8. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals.

    Science.gov (United States)

    Bull, Tim J; Munshi, Tulika; Mikkelsen, Heidi; Hartmann, Sofie B; Sørensen, Maria R; Garcia, Joanna S; Lopez-Perez, Paula M; Hofmann, Sven; Hilpert, Kai; Jungersen, Gregers

    2016-01-01

    The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated "reactor" calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin.

  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. History of the modern epidemiological concept of confounding.

    Science.gov (United States)

    Morabia, Alfredo

    2011-04-01

    The epidemiological concept of confounding has had a convoluted history. It was first expressed as an issue of group non-comparability, later as an uncontrolled fallacy, then as a controllable fallacy named confounding, and, more recently, as an issue of group non-comparability in the distribution of potential outcome types. This latest development synthesised the apparent disconnect between phases of the history of confounding. Group non-comparability is the essence of confounding, and the statistical fallacy its consequence. This essay discusses how confounding was perceived in the 18th and 19th centuries, reviews how the concept evolved across the 20th century and finally describes the modern definition of confounding.

  11. 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....

  12. 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.

  13. 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.

  14. Confounding and exposure measurement error in air pollution epidemiology

    NARCIS (Netherlands)

    Sheppard, L.; Burnett, R.T.; Szpiro, A.A.; Kim, J.Y.; Jerrett, M.; Pope, C.; Brunekreef, B.

    2012-01-01

    Studies in air pollution epidemiology may suffer from some specific forms of confounding and exposure measurement error. This contribution discusses these, mostly in the framework of cohort studies. Evaluation of potential confounding is critical in studies of the health effects of air pollution. Th

  15. Confounding and exposure measurement error in air pollution epidemiology

    NARCIS (Netherlands)

    Sheppard, L.; Burnett, R.T.; Szpiro, A.A.; Kim, J.Y.; Jerrett, M.; Pope, C.; Brunekreef, B.|info:eu-repo/dai/nl/067548180

    2012-01-01

    Studies in air pollution epidemiology may suffer from some specific forms of confounding and exposure measurement error. This contribution discusses these, mostly in the framework of cohort studies. Evaluation of potential confounding is critical in studies of the health effects of air pollution.

  16. Methods to control for unmeasured confounding in pharmacoepidemiology : an overview

    NARCIS (Netherlands)

    Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H.

    2016-01-01

    Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly us

  17. Distinguishing Selection Bias and Confounding Bias in Comparative Effectiveness Research.

    Science.gov (United States)

    Haneuse, Sebastien

    2016-04-01

    Comparative effectiveness research (CER) aims to provide patients and physicians with evidence-based guidance on treatment decisions. As researchers conduct CER they face myriad challenges. Although inadequate control of confounding is the most-often cited source of potential bias, selection bias that arises when patients are differentially excluded from analyses is a distinct phenomenon with distinct consequences: confounding bias compromises internal validity, whereas selection bias compromises external validity. Despite this distinction, however, the label "treatment-selection bias" is being used in the CER literature to denote the phenomenon of confounding bias. Motivated by an ongoing study of treatment choice for depression on weight change over time, this paper formally distinguishes selection and confounding bias in CER. By formally distinguishing selection and confounding bias, this paper clarifies important scientific, design, and analysis issues relevant to ensuring validity. First is that the 2 types of biases may arise simultaneously in any given study; even if confounding bias is completely controlled, a study may nevertheless suffer from selection bias so that the results are not generalizable to the patient population of interest. Second is that the statistical methods used to mitigate the 2 biases are themselves distinct; methods developed to control one type of bias should not be expected to address the other. Finally, the control of selection and confounding bias will often require distinct covariate information. Consequently, as researchers plan future studies of comparative effectiveness, care must be taken to ensure that all data elements relevant to both confounding and selection bias are collected.

  18. Assessment of Confounding in Studies of Delay and Survival

    DEFF Research Database (Denmark)

    Tørring, Marie Louise; Vedsted, Peter; Frydenberg, Morten

    of the influence of delay on survival have been subject to great uncertainties due to unmeasured confounding and measurement error. Systematic evaluation of confounding is needed. AIM: The purpose of this project is to assess confounding in studies of delay and survival in breast cancer patients. We aim to: 1...... delay and survival time in different ways. We therefore assume that the impact of confounding factors depends on the type of delay studied (e.g., patient delay, GP delay, referral delay, or treatment delay). MATERIALS & METHODS: The project includes systematic review and methodological developments...... Pathology Registry, and Statistics Denmark. Among other statistical methods the empirical study will involve use of sensitivity analysis. The statistical analyses will be performed using Stata 9. PERSPECTIVES: A systematic evaluation of confounding will improve our ability to interpret observational studies...

  19. Graphical presentation of confounding in directed acyclic graphs.

    Science.gov (United States)

    Suttorp, Marit M; Siegerink, Bob; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

    2015-09-01

    Since confounding obscures the real effect of the exposure, it is important to adequately address confounding for making valid causal inferences from observational data. Directed acyclic graphs (DAGs) are visual representations of causal assumptions that are increasingly used in modern epidemiology. They can help to identify the presence of confounding for the causal question at hand. This structured approach serves as a visual aid in the scientific discussion by making underlying relations explicit. This article explains the basic concepts of DAGs and provides examples in the field of nephrology with and without presence of confounding. Ultimately, these examples will show that DAGs can be preferable to the traditional methods to identify sources of confounding, especially in complex research questions.

  20. 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.

  1. 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.

  2. 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...

  3. The missing cause approach to unmeasured confounding in pharmacoepidemiology.

    Science.gov (United States)

    Abrahamowicz, Michal; Bjerre, Lise M; Beauchamp, Marie-Eve; LeLorier, Jacques; Burne, Rebecca

    2016-03-30

    Unmeasured confounding is a major threat to the validity of pharmacoepidemiological studies of medication safety and effectiveness. We propose a new method for detecting and reducing the impact of unobserved confounding in large observational database studies. The method uses assumptions similar to the prescribing preference-based instrumental variable (IV) approach. Our method relies on the new 'missing cause' principle, according to which the impact of unmeasured confounding by (contra-)indication may be detected by assessing discrepancies between the following: (i) treatment actually received by individual patients and (ii) treatment that they would be expected to receive based on the observed data. Specifically, we use the treatment-by-discrepancy interaction to test for the presence of unmeasured confounding and correct the treatment effect estimate for the resulting bias. Under standard IV assumptions, we first proved that unmeasured confounding induces a spurious treatment-by-discrepancy interaction in risk difference models for binary outcomes and then simulated large pharmacoepidemiological studies with unmeasured confounding. In simulations, our estimates had four to six times smaller bias than conventional treatment effect estimates, adjusted only for measured confounders, and much smaller variance inflation than unbiased but very unstable IV estimates, resulting in uniformly lowest root mean square errors. The much lower variance of our estimates, relative to IV estimates, was also observed in an application comparing gastrointestinal safety of two classes of anti-inflammatory drugs. In conclusion, our missing cause-based method may complement other methods and enhance accuracy of analyses of large pharmacoepidemiological studies.

  4. Secondary lymphoid tissue chemokine (CCL21) in neuronmicroglia signalling

    NARCIS (Netherlands)

    Biber, Knut; De Jong, Eiko; Vinet, Jonathan; Van Weering, Hilmar; Boddeke, Hendrikus

    2009-01-01

    Microglia is considered to be the sentinel of the CNS. Accordingly, microglia activity aims to protect and to restore, and only in case of uncontrolled or impaired microglia function, these cells may have detrimental effects. The control of microglia activity is thus an important issue to understand

  5. 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.

  6. 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.

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

    Science.gov (United States)

    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.

  8. Methodological problems with population cancer studies: The forgotten confounding factors.

    Science.gov (United States)

    Blaylock, Russell L

    2015-01-01

    Among clinical physicians it is the population study that is considered to be the "gold standard" of medical evidence concerning acceptable treatments. As new information comes to light concerning the many variables and confounding factors that can affect such studies, many older studies lose much of their original impact. While newer population studies take into consideration a far greater number of confounding factors many are still omitted and a number of these omitted factors can have profound effects on interpretation and validity of the study. In this editorial, I will discuss some of the omitted confounding factors and demonstrate how they can alter the interpretation of these papers and their clinical application.

  9. 胸腺原发黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的临床病理特征%Clinicopathologic features of primary thymic extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue type

    Institute of Scientific and Technical Information of China (English)

    孙璐; 石怀银; 韦立新

    2012-01-01

    Objective To study the clinicopathologic features of primary thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Methods The clinical and pathologic findings were evaluated in 3 cases of biopsy confirmed thymic MALT lymphoma. The clincopathologic features,treatment and prognosis were discussed and literatures reviewed.Results One male and two female patients presented with asymptomatic mediastinal masses with a history of Sj(o)gren syndrome.They were aged 36,35 and 41 years respectively,and only one patient had B symptoms.Grossly,all three tumors were encapsulated and had multiple variable-sized cysts on cut-surface.Histopathologically,the normal thymic lobular architecture was effaced by abnormal dense lymphoid infiltration. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating and expanding Hassall's corpuscles and epithelial cyst lining. All cases showed apparent plasmacytic differentiation.Immunhistochemically,the tumor cells were positive for CD20,CD79a,bcl-2 and negative for CD3,CD5,cyclin D1,CD43,CD10,bcl-6,and CD23.The plasma cells showed kappa light chain restriction.Immunoglobulin heavy chain rearrangement in three cases was confirmed by PCR.All patients were at early stage and received routine chemotherapy with or without radiothcrapy aftcr surgical rcmoval.All patients achieved complete remission with 24,18 and 3 months follow-up,respectively. Conclusions Primary thymic MALT lymphoma may be a rare distinctive lymphoma. It can be diagnosed by HE and immunohistochemical study and should be differentiated from reactive lymphoid proliferation,other types of lymphoma and mediastinal thymoma.%目的 探讨胸腺原发黏膜相关淋巴组织(MALT)结外边缘区B细胞淋巴瘤的临床病理特征.方法 对3例经于术切除、病理证实的胸腺原发MALT淋巴瘤病例进行临床病理分析,并复习文献,讨论其临床、病理特征、治疗和预后.结果 3

  10. 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...

  11. 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.

  12. [Application of directed acyclic graphs in control of confounding].

    Science.gov (United States)

    Xiang, R; Dai, W J; Xiong, Y; Wu, X; Yang, Y F; Wang, L; Dai, Z H; Li, J; Liu, A Z

    2016-07-01

    Observational study is a method most commonly used in the etiology study of epidemiology, but confounders, always distort the true causality between exposure and outcome when local inferencing. In order to eliminate these confounding, the determining of variables which need to be adjusted become a key issue. Directed acyclic graph(DAG)could visualize complex causality, provide a simple and intuitive way to identify the confounding, and convert it into the finding of the minimal sufficient adjustment for the control of confounding. On the one hand, directed acyclic graph can choose less variables, which increase statistical efficiency of the analysis. On the other hand, it could help avoiding variables that is not measured or with missing values. In a word, the directed acyclic graph could facilitate the reveal of the real causality effectively.

  13. Confounding and causation in the epidemiology of lead.

    Science.gov (United States)

    Wilson, Ian Harold; Wilson, Simon Barton

    2016-01-01

    The National Health and Medical Research Council recently reported that there were not enough high-quality studies to conclude that associations between health effects and blood lead levels confounding, measurement error and other potential causal factors as common weaknesses. This paper supports those findings with evidence of uncontrolled confounding by parental education, intelligence or household management from several papers. It suggests that inappropriate statistical tests and aggregation of data representing different exposure routes partly explain why confounding has been overlooked. Inadequate correction of confounding has contributed to incorrect conclusions regarding causality at low levels of lead. Linear or log-linear regression models have tended to mask any threshold. While the effects of higher levels of lead exposure are not disputed, overestimation of health effects at low lead exposures has significant implications for policy-makers endeavouring to protect public health through cost-effective regulations.

  14. Hypnotics and mortality – confounding by disease and socioeconomic position

    DEFF Research Database (Denmark)

    Kriegbaum, Margit; Hendriksen, Carsten; Vass, Mikkel

    2015-01-01

    Purpose The aim of this Cohort study of 10 527 Danish men was to investigate the extent to which the association between hypnotics and mortality is confounded by several markers of disease and living conditions. Methods Exposure was purchases of hypnotics 1995–1999 (“low users” (150 or less defined...... point at psychiatric disease, substance abuse and socioeconomic position as potential confounding factors partly explaining the association between use of hypnotics and all-cause mortality....

  15. 贝氏莫尼茨绦虫感染绵羊对小肠局部黏膜淋巴组织的影响%Effect of Moniezia benedeni on Local Mucosal Lymphoid Tissues of Small Intestine in Infected Sheep

    Institute of Scientific and Technical Information of China (English)

    杨祎程; 王雯慧; 祁珊珊; 何晚红; 扎西英派; 张旺东; 张林江

    2012-01-01

    To study the effect of Moniezia benedeni on local mucosal lymphoid tissues of small intestine in natural infected sheep, the intestinal tract of adult sheep (infected group) which natural infected by Moniezia benedeni were observed from macroscopic, microcosmic and sub-microcos-mic scales, and then compared with the normal ones (normal group). The results indicated that the average length of parasite in intestinal tract was 1. 5 m, and the scolex mainly absorbed in the place where there was abundant Peyer's patch of jejunum. Generally, the number of parasite was about 1-2. Opening the jejunum, it was easy to see that themucous membrane which lived by parasite increased thickness and was covered by many gray mucus, and there were also some punctuate hemorrhage on it. The results of microscope showed that the local mucosal epithelium was desquamate, and the number of epithelial cells, intraepithelial lymphocyte and goblet cells were all increased obviously under the integral mucosal epithelium; there were hyperemia in capillaries of lamina propria, and hyperplasia of lymphocyte, plasmocyte, diffuse lymphoid tissue and gobletcells of intestinal gland happened in different degree. There also had mortification in the part of intestinal gland in the place which located by scolex; under the mucous membrane, there was obvious hyperplasia in lymphatic nodules and Peyer's patch? And part of this hyperplasia that protruded into lamina propria could form some new dome areas; There were a great quantity of eosinophilic granulocytes infiltrated among lamina propria, mucosal substratum and mucosal layers. Under scanning electron microscope, the mucosal epithelium of intestine was desquamate in infected group; The scolex which was covered with layer of compact microvillus of Moniezia be-nedeni was ellipsoid and had four sucking disk but without rostellum and canaliculus. The findings suggested that the thickening of intestinal mucous membrane was mainly caused by hyperplasia of

  16. Environmental confounding in gene-environment interaction studies.

    Science.gov (United States)

    Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

    2013-07-01

    We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

  17. Using an instrumental variable to test for unmeasured confounding.

    Science.gov (United States)

    Guo, Zijian; Cheng, Jing; Lorch, Scott A; Small, Dylan S

    2014-09-10

    An important concern in an observational study is whether or not there is unmeasured confounding, that is, unmeasured ways in which the treatment and control groups differ before treatment, which affect the outcome. We develop a test of whether there is unmeasured confounding when an instrumental variable (IV) is available. An IV is a variable that is independent of the unmeasured confounding and encourages a subject to take one treatment level versus another, while having no effect on the outcome beyond its encouragement of a certain treatment level. We show what types of unmeasured confounding can be tested for with an IV and develop a test for this type of unmeasured confounding that has correct type I error rate. We show that the widely used Durbin-Wu-Hausman test can have inflated type I error rates when there is treatment effect heterogeneity. Additionally, we show that our test provides more insight into the nature of the unmeasured confounding than the Durbin-Wu-Hausman test. We apply our test to an observational study of the effect of a premature infant being delivered in a high-level neonatal intensive care unit (one with mechanical assisted ventilation and high volume) versus a lower level unit, using the excess travel time a mother lives from the nearest high-level unit to the nearest lower-level unit as an IV.

  18. Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.

    Science.gov (United States)

    Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H

    2016-06-01

    Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly used methods to detect or control for unmeasured confounding and to provide recommendations for proper application in pharmacoepidemiology. Methods/Results Methods to control for unmeasured confounding in the design phase of a study are case only designs (e.g., case-crossover, case-time control, self-controlled case series) and the prior event rate ratio adjustment method. Methods that can be applied in the data analysis phase include, negative control method, perturbation variable method, instrumental variable methods, sensitivity analysis, and ecological analysis. A separate group of methods are those in which additional information on confounders is collected from a substudy. The latter group includes external adjustment, propensity score calibration, two-stage sampling, and multiple imputation. Conclusion As the performance and application of the methods to handle unmeasured confounding may differ across studies and across databases, we stress the importance of using both statistical evidence and substantial clinical knowledge for interpretation of the study results.

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  6. File list: Pol.Bld.20.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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

    Science.gov (United States)

    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. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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...

  13. 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

  14. 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

  15. Opportunities for minimization of confounding in observational research.

    Science.gov (United States)

    Quartey, George; Feudjo-Tepie, Maurille; Wang, Jixian; Kim, Joseph

    2011-01-01

    Observational epidemiological studies are increasingly used in pharmaceutical research to evaluate the safety and effectiveness of medicines. Such studies can complement findings from randomized clinical trials by involving larger and more generalizable patient populations by accruing greater durations of follow-up and by representing what happens more typically in the clinical setting. However, the interpretation of exposure effects in observational studies is almost always complicated by non-random exposure allocation, which can result in confounding and potentially lead to misleading conclusions. Confounding occurs when an extraneous factor, related to both the exposure and the outcome of interest, partly or entirely explains the relationship observed between the study exposure and the outcome. Although randomization can eliminate confounding by distributing all such extraneous factors equally across the levels of a given exposure, methods for dealing with confounding in observational studies include a careful choice of study design and the possible use of advanced analytical methods. The aim of this paper is to introduce some of the approaches that can be used to help minimize the impact of confounding in observational research to the reader working in the pharmaceutical industry.

  16. ‘Mechanical restraint—confounders, risk, alliance score’

    DEFF Research Database (Denmark)

    Nielsen, Lea Deichmann; Bech, Per; Hounsgaard, Lise

    2017-01-01

    Background: Unstructured risk assessment, as well as confounders (underlying reasons for the patient’s risk behaviour and alliance), risk behaviour, and parameters of alliance, have been identified as factors that prolong the duration of mechanical restraint among forensic mental health inpatients....... Aim: To clinically validate a new, structured short-term risk assessment instrument called the Mechanical Restraint–Confounders, Risk, Alliance Score (MR-CRAS), with the intended purpose of supporting the clinicians' observation and assessment of the patient’s readiness to be released from mechanical...... restraint. Methods: The content and layout of MR-CRAS and its user manual were evaluated using face validation by forensic mental health clinicians, content validation by an expert panel, and pilot testing within two, closed forensic mental health inpatient units. Results: The three sub-scales (Confounders...

  17. Confounding adjustment through front-door blocking in longitudinal studies

    Directory of Open Access Journals (Sweden)

    Arvid Sjölander

    2013-03-01

    Full Text Available A common aim of epidemiological research is to estimate the causal effect of a particular exposure on a particular outcome. Towards this end, observed associations are often ‘adjusted’ for potential confounding variables. When the potential confounders are unmeasured, explicit adjustment becomes unfeasible. It has been demonstrated that causal effects can be estimated even in the presence of umeasured confounding, utilizing a method called ‘front-door blocking’. In this paper we generalize this method to longitudinal studies. We demonstrate that the method of front-door blocking poses a number of challenging statistical problems, analogous to the famous problems associ- ated with the method of ‘back-door blocking’.

  18. 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.

  19. 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.

  20. Air Pollution and Autism Spectrum Disorders: Causal or Confounded?

    Science.gov (United States)

    Weisskopf, Marc G; Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L

    2015-12-01

    In the last decade, several studies have examined the association between perinatal exposure to ambient air pollution and risk of autism spectrum disorder (ASD). These studies have largely been consistent, with associations seen with different aspects of air pollution, including hazardous air toxics, ozone, particulate, and traffic-related pollution. Confounding by socioeconomic status (SES) and place of residence are of particular concern, as these can be related to ASD case ascertainment and other potential causal risk factors for ASD. While all studies take steps to address this concern, residual confounding is difficult to rule out. Two recent studies of air pollution and ASD, however, present findings that strongly argue against residual confounding, especially for factors that do not vary over relatively short time intervals. These two studies, conducted in communities around the USA, found a specific association with air pollution exposure during the 3rd, but not the 1st, trimester, when both trimesters were modeled simultaneously. In this review, we discuss confounding possibilities and then explain-with the aid of directed acyclic graphs (DAGs)-why an association that is specific to a particular time window, when multiple exposure windows are simultaneously assessed, argues against residual confounding by (even unmeasured) non-time-varying factors. In addition, we discuss why examining ambient air pollution concentration as a proxy for personal exposure helps avoid confounding by personal behavior differences, and the implications of measurement error in using ambient concentrations as a proxy for personal exposures. Given the general consistency of findings across studies and the exposure-window-specific associations recently reported, the overall evidence for a causal association between air pollution and ASD is increasingly compelling.

  1. CONFOUNDING STRUCTURE OF TWO-LEVEL NONREGULAR FACTORIAL DESIGNS

    Institute of Scientific and Technical Information of China (English)

    Ren Junbai

    2012-01-01

    In design theory,the alias structure of regular fractional factorial designs is elegantly described with group theory.However,this approach cannot be applied to nonregular designs directly. For an arbitrary nonregular design,a natural question is how to describe the confounding relations between its effects,is there any inner structure similar to regular designs? The aim of this article is to answer this basic question.Using coefficients of indicator function,confounding structure of nonregular fractional factorial designs is obtained as linear constrains on the values of effects.A method to estimate the sparse significant effects in an arbitrary nonregular design is given through an example.

  2. 眼眶及眼附属器黏膜相关B细胞淋巴瘤中BCL10表达和染色体易位的检测%Abnormal BCL10 nuclear expression and chromosomal translocation in ocular adnexal mucosa-associated lymphoid tissue lymphomas

    Institute of Scientific and Technical Information of China (English)

    李百周; 杨文涛; 周晓燕; 范月珍; 陆洪芬; 施达仁

    2008-01-01

    Objective To detect the BCL10 expression and several types of chromosomal translocations [including t (11 ;18)/API2-MALT1 ; t (1 ;14)/IgH- BCL10 and t (14;18)/MALTI-IgH] in ocular adnexal mucosa-associated lymphoid tissue lymphomas (OA-MALT lymphomas). Methods Sixty OA-MALT lymphomas were collected from Cancer Hospital of Fudan University. BCLIO was detected by immunohistochemical studies, and API2-MALT1 fusion gene, BCLIO, MALT1 and IgH chromosomal abnormalities were detected by fluorescent in situ hybridization ( FISH). Fisher's exact test was used to analyze the relation between nuclear BCL10 expression and chromosomal translocation. Results BCL10 expressed in 85.0% (51/60) OA-MALT lymphomas. Among these positive cases, 25 cases (41.7%) were expressed in the cytoplasm, and 26 cases (43.3%) were expressed in the nucleus. FISH results showed that no chromosomal abnormalities related with BCL10 and IgH genes, except 2 cases with API2-MALT1 fusion gene. Under statistic of Fisher exact test, nuclear BCL10 expression and API2-MALT1 fusion gene were two independent factors ( P > 0.05 ). Conclusions BCL10 nuclear expression is common in OAMALT lymphomas and may be used as a potential marker for the diagnosis of MALT lymphomas arising from ocular adnexa. Aberrant chromosomal translocations reported in the other sites MALT lymphomas are rare in OA-MALT lymphomas.%目的 研究眼眶及眼附属器黏膜相关(OA-MALT)淋巴瘤中BCL10蛋白表达及染色体易位情况.方法 收集60例OA-MALT淋巴瘤患者的标本,采用免疫组织化学法检测BCL10蛋白的表达,用荧光素原位杂交(FISH)法分别检测AP12-MALT1融合基因、BCL10、MALT1及IgH基因的异常.采用交叉分组设计,对结果进行Fisher精确检验.结果 OA-MALT淋巴瘤中BCLI0蛋白表达的阳性率为85.0%(51/60),其中胞质阳性率为41.7%(25/60),胞核阳性率为43.3%(26/60).FISH结果显示除2例患者有API2.MALTI融合基因外,其余患者的BCL10基因和IgH基

  3. Prevalence of API2-MALT1 fusion gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas and diffuse large B cell lymphomas%胃肠道黏膜相关边缘区B细胞淋巴瘤和弥漫性大B细胞淋巴瘤中API2-MALT1融合基因表达的差异

    Institute of Scientific and Technical Information of China (English)

    李百周; 陆洪芬; 盛伟琪; 施达仁

    2009-01-01

    Objective To investigate the difference of the prevalence of t(11;18) (q21;q21)/ AP12-MALT1 fusion gene between gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL). Methods A total of 57 cases gastrointestinal MALT lymphomas (38 gastric and 19 intestinal lymphomas), 32 DLBCL (28 gastric and 4 intestinal lymphomas) and 7 cases gastric DLBCL accompanied MALT lymphoma were collected from the Cancer Hospital of Fudan University. API2-MALT1 fusion gene was detected by fluorescent in situ hybridization (FISH) using both dual fusion translocation and break apart probes. Results Among gastrointestinal MALT lymphomas, API2-MALT1 fusion gene was found in 12 of 57 cases (21.1% , 10 gastric and 2 intestinal lymphomas). In contrast, the fusion gene was not found in all 32 DLBCL and 7 gastric DLBCL with MALT lymphoma component. There was statistical significant difference between two groups (X~2=9.383, P=0.001). Conclusions API2-MALT1 fusion gene is a distinctive genetic aberration in MALT lymphomas, and is not present in DLBCL. The findings suggest that gastrointestinal tract MALT lymphomas with API2-MALT1 fusion geue may not transform into DLBCL, which may represent primary lymphoma or transformed API2-MALT1 negative MALT lymphomas.%目的 比较t(11;18)(q21;q21)/API2-MALX1融合基因在胃肠道黏膜相关边缘区B细胞淋巴瘤(MALN淋巴瘤)和弥漫性大B细胞淋巴瘤(DLBCL)中的发生情况,探讨t(11;18)(q21;q21)与胃肠道MALT淋巴瘤和DLBCL间演进的关系.方法 收集57例胃肠道MALT淋巴瘤(包括38例胃和19例肠),32例胃肠道DLBCL(包括28例胃和4例肠)和7例胃DLBCL同时合并MALT淋巴瘤成分,用荧光原位杂交(FISH)检测API2-MALT1融合基因.使用的探针包括API2-MALT1双色融合易位探针和MALT1双色分离重排探针.结果 在MALT淋巴瘤中有21.1%(12/57,包括10例胃和2例肠)发现API2-MALT1融合基因,而在32例DLBCL和7例DLBCL与MALT淋巴瘤混合

  4. 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.

  5. 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.

  6. Cascaded discrimination of normal, abnormal, and confounder classes in histopathology: Gleason grading of prostate cancer

    Directory of Open Access Journals (Sweden)

    Doyle Scott

    2012-10-01

    Full Text Available Abstract Background Automated classification of histopathology involves identification of multiple classes, including benign, cancerous, and confounder categories. The confounder tissue classes can often mimic and share attributes with both the diseased and normal tissue classes, and can be particularly difficult to identify, both manually and by automated classifiers. In the case of prostate cancer, they may be several confounding tissue types present in a biopsy sample, posing as major sources of diagnostic error for pathologists. Two common multi-class approaches are one-shot classification (OSC, where all classes are identified simultaneously, and one-versus-all (OVA, where a “target” class is distinguished from all “non-target” classes. OSC is typically unable to handle discrimination of classes of varying similarity (e.g. with images of prostate atrophy and high grade cancer, while OVA forces several heterogeneous classes into a single “non-target” class. In this work, we present a cascaded (CAS approach to classifying prostate biopsy tissue samples, where images from different classes are grouped to maximize intra-group homogeneity while maximizing inter-group heterogeneity. Results We apply the CAS approach to categorize 2000 tissue samples taken from 214 patient studies into seven classes: epithelium, stroma, atrophy, prostatic intraepithelial neoplasia (PIN, and prostate cancer Gleason grades 3, 4, and 5. A series of increasingly granular binary classifiers are used to split the different tissue classes until the images have been categorized into a single unique class. Our automatically-extracted image feature set includes architectural features based on location of the nuclei within the tissue sample as well as texture features extracted on a per-pixel level. The CAS strategy yields a positive predictive value (PPV of 0.86 in classifying the 2000 tissue images into one of 7 classes, compared with the OVA (0.77 PPV and OSC

  7. The Threshold of Embedded M Collider Bias and Confounding Bias

    Science.gov (United States)

    Kelcey, Benjamin; Carlisle, Joanne

    2011-01-01

    Of particular import to this study, is collider bias originating from stratification on retreatment variables forming an embedded M or bowtie structural design. That is, rather than assume an M structural design which suggests that "X" is a collider but not a confounder, the authors adopt what they consider to be a more reasonable…

  8. The relation of collapsibility and confounding to faithfulness and stability.

    Science.gov (United States)

    Mansournia, Mohammad Ali; Greenland, Sander

    2015-07-01

    A probability distribution may have some properties that are stable under a structure (e.g., a causal graph) and other properties that are unstable. Stable properties are implied by the structure and thus will be shared by populations following the structure. In contrast, unstable properties correspond to special circumstances that are unlikely to be replicated across those populations. A probability distribution is faithful to the structure if all independencies in the distribution are logical consequences of the structure. We explore the distinction between confounding and noncollapsibility in relation to the concepts of faithfulness and stability. Simple collapsibility of an odds ratio over a risk factor is unstable and thus unlikely if the exposure affects the outcome, whether or not the risk factor is associated with exposure. For a binary exposure with no effect, collapsibility over a confounder also requires unfaithfulness. Nonetheless, if present, simple collapsibility of the odds ratio limits the degree of confounding by the covariate. Collapsibility of effect measures is stable if the covariate is independent of the outcome given exposure, but it is unstable if the covariate is an instrumental variable. Understanding stable and unstable properties of distributions under causal structures, and the distinction between stability and faithfulness, yields important insights into the correspondence between noncollapsibility and confounding.

  9. 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.

  10. 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

  11. 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.   

  12. 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.

  13. 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.

  14. Simultaneous dimension reduction and adjustment for confounding variation.

    Science.gov (United States)

    Lin, Zhixiang; Yang, Can; Zhu, Ying; Duchi, John; Fu, Yao; Wang, Yong; Jiang, Bai; Zamanighomi, Mahdi; Xu, Xuming; Li, Mingfeng; Sestan, Nenad; Zhao, Hongyu; Wong, Wing Hung

    2016-12-20

    Dimension reduction methods are commonly applied to high-throughput biological datasets. However, the results can be hindered by confounding factors, either biological or technical in origin. In this study, we extend principal component analysis (PCA) to propose AC-PCA for simultaneous dimension reduction and adjustment for confounding (AC) variation. We show that AC-PCA can adjust for (i) variations across individual donors present in a human brain exon array dataset and (ii) variations of different species in a model organism ENCODE RNA sequencing dataset. Our approach is able to recover the anatomical structure of neocortical regions and to capture the shared variation among species during embryonic development. For gene selection purposes, we extend AC-PCA with sparsity constraints and propose and implement an efficient algorithm. The methods developed in this paper can also be applied to more general settings. The R package and MATLAB source code are available at https://github.com/linzx06/AC-PCA.

  15. Addressing Confounding in Predictive Models with an Application to Neuroimaging.

    Science.gov (United States)

    Linn, Kristin A; Gaonkar, Bilwaj; Doshi, Jimit; Davatzikos, Christos; Shinohara, Russell T

    2016-05-01

    Understanding structural changes in the brain that are caused by a particular disease is a major goal of neuroimaging research. Multivariate pattern analysis (MVPA) comprises a collection of tools that can be used to understand complex disease efxcfects across the brain. We discuss several important issues that must be considered when analyzing data from neuroimaging studies using MVPA. In particular, we focus on the consequences of confounding by non-imaging variables such as age and sex on the results of MVPA. After reviewing current practice to address confounding in neuroimaging studies, we propose an alternative approach based on inverse probability weighting. Although the proposed method is motivated by neuroimaging applications, it is broadly applicable to many problems in machine learning and predictive modeling. We demonstrate the advantages of our approach on simulated and real data examples.

  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. 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.

  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. Air pollutants and health outcomes: Assessment of confounding by influenza

    Science.gov (United States)

    Thach, Thuan-Quoc; Wong, Chit-Ming; Chan, King-Pan; Chau, Yuen-Kwan; Neil Thomas, G.; Ou, Chun-Quan; Yang, Lin; Peiris, Joseph S. M.; Lam, Tai-Hing; Hedley, Anthony J.

    2010-04-01

    We assessed confounding of associations between short-term effects of air pollution and health outcomes by influenza using Hong Kong mortality and hospitalization data for 1996-2002. Three measures of influenza were defined: (i) intensity: weekly proportion of positive influenza viruses, (ii) epidemic: weekly number of positive influenza viruses ≥4% of the annual number for ≥2 consecutive weeks, and (iii) predominance: an epidemic period with co-circulation of respiratory syncytial virus influenza on associations between nitrogen dioxide (NO 2), sulfur dioxide (SO 2), particulate matter with aerodynamic diameter ≤10 μm (PM 10) and ozone (O 3) and health outcomes including all natural causes mortality, cardiorespiratory mortality and hospitalization. Generalized additive Poisson regression model with natural cubic splines was fitted to control for time-varying covariates to estimate air pollution health effects. Confounding with influenza was assessed using an absolute difference of >0.1% between unadjusted and adjusted excess risks (ER%). Without adjustment, pollutants were associated with positive ER% for all health outcomes except asthma and stroke hospitalization with SO 2 and stroke hospitalization with O 3. Following adjustment, changes in ER% for all pollutants were 0.1% for mortality from stroke with NO 2 and SO 2, cardiac or heart disease with NO 2, PM 10 and O 3, lower respiratory infections with NO 2 and O 3 and mortality from chronic obstructive pulmonary disease with all pollutants. Changes >0.1% were seen for acute respiratory disease hospitalization with NO 2, SO 2 and O 3 and acute lower respiratory infections hospitalization with PM 10. Generally, influenza does not confound the observed associations of air pollutants with all natural causes mortality and cardiovascular hospitalization, but for some pollutants and subgroups of cardiorespiratory mortality and respiratory hospitalization there was evidence to suggest confounding by influenza.

  20. Causal diagrams and multivariate analysis III: confound it!

    Science.gov (United States)

    Jupiter, Daniel C

    2015-01-01

    This commentary concludes my series concerning inclusion of variables in multivariate analyses. We take up the issues of confounding and effect modification and summarize the work we have thus far done. Finally, we provide a rough algorithm to help guide us through the maze of possibilities that we have outlined. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

    Directory of Open Access Journals (Sweden)

    Enrica Migliore

    Full Text Available Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR and 95% confidence intervals (CI were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07-1.47] to 1.10 [0.94-1.30] in the first, and from 1.26 [1.08-1.47] to 1.10 [0.93-1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache revealed no increased risk of wheezing in children.The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.

  4. 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.

  5. Quantification of confounding factors in MRI-based dose calculations as applied to prostate IMRT

    Science.gov (United States)

    Maspero, Matteo; Seevinck, Peter R.; Schubert, Gerald; Hoesl, Michaela A. U.; van Asselen, Bram; Viergever, Max A.; Lagendijk, Jan J. W.; Meijer, Gert J.; van den Berg, Cornelis A. T.

    2017-02-01

    Magnetic resonance (MR)-only radiotherapy treatment planning requires pseudo-CT (pCT) images to enable MR-based dose calculations. To verify the accuracy of MR-based dose calculations, institutions interested in introducing MR-only planning will have to compare pCT-based and computer tomography (CT)-based dose calculations. However, interpreting such comparison studies may be challenging, since potential differences arise from a range of confounding factors which are not necessarily specific to MR-only planning. Therefore, the aim of this study is to identify and quantify the contribution of factors confounding dosimetric accuracy estimation in comparison studies between CT and pCT. The following factors were distinguished: set-up and positioning differences between imaging sessions, MR-related geometric inaccuracy, pCT generation, use of specific calibration curves to convert pCT into electron density information, and registration errors. The study comprised fourteen prostate cancer patients who underwent CT/MRI-based treatment planning. To enable pCT generation, a commercial solution (MRCAT, Philips Healthcare, Vantaa, Finland) was adopted. IMRT plans were calculated on CT (gold standard) and pCTs. Dose difference maps in a high dose region (CTV) and in the body volume were evaluated, and the contribution to dose errors of possible confounding factors was individually quantified. We found that the largest confounding factor leading to dose difference was the use of different calibration curves to convert pCT and CT into electron density (0.7%). The second largest factor was the pCT generation which resulted in pCT stratified into a fixed number of tissue classes (0.16%). Inter-scan differences due to patient repositioning, MR-related geometric inaccuracy, and registration errors did not significantly contribute to dose differences (0.01%). The proposed approach successfully identified and quantified the factors confounding accurate MRI-based dose calculation in

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 不同浓度次级淋巴组织趋化因子对溃疡性结肠炎大鼠淋巴细胞迁移的影响及其意义%Impact of secondary lymphoid tissue chemokine on lymphocyte migration and the significance thereof in pathogenesis of ulcerative colitis: experiment with rats

    Institute of Scientific and Technical Information of China (English)

    葛步军; 陈锡美; 杨长青; 吴剑

    2008-01-01

    Objective To explore the impact of secondary lymphoid tissue chemokine (SLC) on lymphocyte migration and the significance thereof in the pathogenesis of ulcerative colitis (UC). Methods Sixty SD rats were randomly divided into 3 equal groups: model group undergoing dripping of 40% acetone solution of dinitro-chlorobenzene (DNCB) on the back for 2 weeks and then enema of 6% DNCB acetone solution so as to establish models of UC, and then intravenous injection of normal saline (NS) for 5 days; SLC antibody intervention group undergoing intravenous injection of SLC antibody 15 μg· ml-1· kg-1 immediately after the establishing of model; and control group undergoing enema of NS nly and then intravenous injection of NS for 5 days. Six days after the establishing of model venous blood samples were collected from the portal veins of the 3 groups. Lymphocytes were isolated and cultured. RT-PCR was used to detect the mRNA expression of the SLC receptor CCR7. Boyden chamber system was used to examine the migration ability of the lymphocytes exposed to SLC of 20, 40, 60, 80, and 100 ng/ml respectively. ELISA was used to detect the expression of interleukin (IL) -10 and interferon (IFN) -γ in the supomatants of the lymphocytes of different groups. Results RT-PCR showed that the CCR7 mRNA expression level of the model group was (0. 792±0. 108), significantly higher than that of the intervention group (0. 386±0. 115, P =0. 0429), and the CCR7 mRNA expression levels of these 2 groups were both significantly higher than that of the control group (0. 106±0. 029, both P < 0. 01). SLC dese-dependently promoted the migration ability of the lymphocytes, but there existed a saturation phenomenon. Exposed to 80 ng/ml SLC the migration level of the iymphocytes of the model group peaked to (85.9±16.0), 3.7 times as high as that of the control group (20. 5±1.8, P < 0. 01), and the migration level of the lymphocytes of the intervention group was 38. 2±6. 3, significantly higher than

  11. 中国南方地区原发性眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤分子遗传学异常%Study on genetic aberrations of ocular mucosa-associated lymphoid tissue lymphomas occurring in southern China

    Institute of Scientific and Technical Information of China (English)

    张雪梅; 叶洪涛; 张文燕; 周元平; 莫祥兰; 李永平; 王桂秋; 周英琼; 曾思恩; 李甘地

    2010-01-01

    Objective To study the genetic aberrations of ocular extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occurring in patients from southern China.Methods Fifty seven paraffin-embedded ocular MALT lymphoma specimens from patients in southern China were studied by interphase fluorescence-in-situ hybridization (FISH) for genetic aberrations including t(11;18) (q21;q21)/API2-MALT1, t(1;14) (p22;q32)/IgH-bcl-10, t(14;18) (q32;q21)/IgH-MALT1 and bcl-6/FOXP1 gene translocations. Results Amongst the 57 cases studied, 9 cases ( 15.8% ) showed chromosome translocations, including 4 cases ( 7.0% ) of t ( 11; 18 ) ( q21; q21 )/API2-MALT1, 1 case ( 1.8% ) of t ( 14; 18 ) ( q32; q21 )/IgH-MALT1, 1 case ( 1.8% ) of bcl-6 gene-related chromosome translocation and 3 cases (5.3% ) of IgH-unknown translocation partner. FISH revealed 17 cases (29.8%)with 3 copies of bcl-6 gene, 21 cases (36. 8% ) with 3 copies of MALT1 gene and 12 cases (21.1%) with 3 copies of both genes. Conclusions The MALT lymphoma-associated chromosome translocations t (11 ;18)(q21;q21 )/API2-MALT1 and t (14; 18) (q32; q21 )/IgH-MALT1 are demonstrated in ocular MALT lymphomas of southern Chinese patients. The prevalence is significantly different from that reported in northern Chinese and northern American patients, indicating a geographic heterogeneity in the MALT lymphoma-associated genetic aberrations. The presence of 3 copies of bcl-6 and MALT1 genes is the commonest genetic abnormalities observed in ocular MALT lymphomas, suggesting a possible role in MALT lymphomagenesis.%目的 探讨中国南方地区原发性眼附属器黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(简称MALT淋巴瘤)分子遗传学异常的发生情况.方法应用间期荧光原位杂交(FISH)方法,检测57例来自中国南方部分地区眼附属器MALT淋巴瘤病例组织中t(11;18)(q21;q21)/API2-MALT1、t(1;14)(p22;q32)/IgH-bcl-10、t(14;18)(q32;q21)/IgH-MALT1以及涉及bcl-6

  12. High incidence of t(11;18)/API2-MALT1 and BCL10 aberrant nuclear expression in pulmonary mucosa-associated lymphoid tissue lymphomus%肺黏膜相关B淋巴细胞淋巴瘤中BCL10蛋白表达和染色体易位的关系

    Institute of Scientific and Technical Information of China (English)

    李百周; 杨文涛; 陆洪芬; 范月珍; 周晓燕; 施达仁

    2008-01-01

    Objective To detect the BCL10 expression and chromosomal translocations in pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas, including t (11;18)/API2-MALT1 ; t(1 ;14)/IgH-BCLI0 and t(14;18)/MALTI-IgH, and to determine if aberrant nuclear BCL10 expression is related with chromosomal translocations. Methods Twenty-three cases of pulmonary MALT lymphomas were collected from Cancer Hospital of Fudan University. BCLIO was detected by immunohistoehemistry of EnVision method, and API2.-MALT1, BCLI0, MALTI, IgH chromosomal abnormalities were detected by fluorescent in situ hybridization (FISH) technique. Results BCLI0 was expressed in 82. 6% (19/23) of the pulmonary MALT lymphomas. Among those eases, 9 of 23 (39.1%) were expressed in the cytoplasm, and 10 of 23 (43.5%) were in the nucleus. In the FISH results, 9 cases (39.1%, 9/23) showed API2MALT1 fusion gene, 1 case with possible BCLI0-IgH abnormality, but none showed chromosomal abnormalities related with MALTI and IgH gene simultaneously. Among 10 BCL10 nuclear expressive cases only 5 harbored genetic abnormalities. There was no correlation between BCL10 abrerrant nuclear expression and chromosoma(translocations) (X2=0.306,P=0.685). Follow-up of 10 eases for a period of 7 to 35 months showed that all the patients were alive. Because different treatments applied in different patients(chemotherapy only, surgery with chemotherapy or surgery only), best available treatment could not be confirmed in this study. Conclusions t (11;18)/API2-MALT1 was the most common chromosomal abnormality in pulmonary MALT lymphomas, but t(1;14)/BCLI0-IgH and t(14; 18)/MALTl-lgH were rare. Pulmonary MALT lymphomas also had higher nuclear BCLI0 expression, which was not correlated with chromosomal abnormalities. As a result, BCLIO nuclear expression and cytogenetic aberration may be helpful in the diagnosis, especially for small biopsy specimens.%目的 检测肺黏膜相关B淋巴细胞淋巴瘤(MALT淋巴瘤)中BCL10蛋白表达

  13. A clinical study of chromosome translocations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in Chinese patients%中国人黏膜相关淋巴组织结外边缘区淋巴瘤染色体易位的临床研究

    Institute of Scientific and Technical Information of China (English)

    董格红; 冯振博; 高子芬; 叶洪涛; 王桂秋; 宫丽平; 王晋芬; 莫祥兰; 刘红刚; 董丽娜; 周英琼; 张雪梅

    2009-01-01

    Objective To investigate the genetic aberrations in extranodal marginal zone lymphoma of mueosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. Methods Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t(11; 18) (q21;q21)/API2-MALT1, t(1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. Results These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t(11;18) (q21;q21) API2-MALT1 13% (29/217), t (1;14)(p22 ;q32) IGH-BCLIO in 1% (3/217), t(14;18) (q32;q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t(11; 18) (q21;q21)API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47% , 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6% , 4/68). t(1 ;14) (p22;q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t(14;18) (q32;q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17% , 1/6) and stomach (4%, 3/84). Conclusions It is demonstrated that the four translocatidns occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.%目的 探讨中国人不同部位黏膜相关淋巴组织结外边缘区淋巴瘤(MALTL)中分子遗传学异常的发生情况.方法 应用间期荧光原位杂交(FISH)方法,检测217例不同部位MALTL的t(11;18)(q21;q21)/API2-MALT1、t(1;14)(p22;q32)/IGH-BCL10、t(14;18)(q32;q21)/IGH-MALT1和涉及BCL6基因的染色体易位.结果 染色

  14. 77例胃的黏膜相关淋巴组织淋巴瘤的临床分析%Clinical outcome and prognostic factors of primary gastric mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 77 cases

    Institute of Scientific and Technical Information of China (English)

    王淑莲; 李晔雄; 宋永文; 金晶; 王维虎; 刘跃平; 刘新帆; 余子豪

    2009-01-01

    目的 回顾分析原发于胃的黏膜相关淋巴组织淋巴瘤(MALT)的治疗结果、预后因素和失败类型.方法 搜集20余年间收治的原发胃MALT淋巴瘤病例,病理证实且为Ⅰ、Ⅱ、ⅡE期.77例患者进入分析,手术切除组60例(手术14例、手术+化疗32例、手术+化放疗4例、手术+放疗9例、化疗+手术+化疗1例),非手术切除组17例(化放疗11例、化疗5例、放疗1例).放疗采用常规放疗(20例)和三维适形放疗(5例).化疗采用CHOP、BACOP或COP方案(53例).结果 随访1~198个月,中位值57个月.全组患者5年总生存率为74%,5年无瘤生存率为70%,5年局部控制率为76%,5年无远处失败生存率为87%.单因素分析显示临床分期与总生存率显著相关(P=0.02),肿瘤大小(P=0.03)和手术程度(P=0.02)与无瘤生存率显著相关,临床分期(P=0.04)、肿瘤大小(P=0.01)和手术程度(P=0.03)与局部控制率显著相关,未发现与无远处失败生存率显著相关因素.Ⅰ、Ⅱ期患者手术治疗后失败主要在远处,非手术治疗患者的失败主要在局部.ⅡE期患者,无论手术组还是非手术组,失败主要在局部.结论 胃原发黏膜组织相关淋巴瘤采用手术和非手术治疗均可取得很好的治疗效果,临床分期是非常重要的预后因素.%Objective To analyze the clinical results and prognostic factors of patients with early-stage primary gastric mucosa-associated lymphoid tissue(MALT) lymphoma. Methods Seventy-seven pa-tients with primary gastric MALT lymphoma treated from 1985 to 2006 were retrospectively analyzed. All pa-tients were pathologically confirmed as MALT lymphoma in stage Ⅰ ,Ⅱ and ⅡE (by modified Blackedge staging system). Thirty-seven patients had stage Ⅰ disease,23 stage Ⅱ and 17 stage ⅡE. Sixty patients un-derwent surgical resection and 17 received non-surgical treatment. Survival rates were calculated by the Kap-lan-Meier analysis with the Logrank test. Results With a median

  15. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    Directory of Open Access Journals (Sweden)

    Anne-Christin Hauschild

    2015-06-01

    Full Text Available Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD. While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD

  16. 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.

  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. 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.

  19. 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

  20. 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

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

    Science.gov (United States)

    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

  2. 不同部位黏膜相关淋巴组织结外边缘区B细胞淋巴瘤中染色体的异常及其意义%Frequency of genetic aberrations in mueesa-assoelated lymphoid tissue lymphoma of different sites

    Institute of Scientific and Technical Information of China (English)

    李百周; 陆洪芬; 周晓燕; 杨文涛; 孔蕴毅; 范月珍; 施达仁

    2008-01-01

    目的 探讨不同部位黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT淋巴瘤)中t(11;18)/APl2-MALT1、t(1;14)/IgH-bcl-10、t(14;18)/IgH-MALT1和其他遗传学异常的发生情况及其意义.方法 收集196例不同部位的MALT淋巴瘤,包括胃53例[其中9例有弥漫性大B细胞淋巴瘤(DLBCL)成分]、眼眶50例、涎腺20例、肺20例、肠17例、皮肤17例、肝脏8例、甲状腺5例和其他部位6例(包括舌根2例,胰腺、喉、声带和肾脏各1例),用荧光原位杂交(FISH)分别检测APl2-MALT1、bel-10、MALT1和IgH基因的异常.结果 在196例MALT淋巴瘤中,APl2-MALT1融合基因共检出25例(12.8%).但是在不同部位,阳性率差异有统计学意义(P=0.002):从高到低依次为肺(45.0%,9/20)、不伴DLBCL成分的胃MALT淋巴瘤(22.7%,10/44)、涎腺(15.0%,3/20)、肠2/17、眼眶2.0%(1/50).而在伴DLBCL成分的胃MALT淋巴瘤、皮肤、甲状腺、肝脏和其他散发部位均未发现APl2-MALT1融合基因.在196例中,1例肺MALT淋巴瘤同时显示IgH基因和MALT1基因异常,可能是t(14;18)/IgH-MALT1异常.3例(2例不伴DLBCL成分的胃和1例肺)同时显示IgH基因和bcl-10基因异常,可能是t(1;14)/IgH-bcl-10异常.此外,用MALT1基因探针检测中,6例(2例涎腺、2例肝脏、1例伴DLBCL成分的胃和1例甲状腺)可能为18号染色体3体;3例(2例胃和1例肠)为MALT1基因扩增.结论 在MALT淋巴瘤中特异性的染色体异常发生率较低,但在不同部位,这些异常发生率存在差异.该现象提示发生在不同部位的MALT淋巴瘤,尽管组织形态学特点类似,但可能具有不同的发病机制.%Objective To study the frequency of certain specific genetic aberrations, including t(11;18)/API2-MALT1, t(1;14)/IgH-I-bcl-10 and t(14;18)/IgH-I-MALT1, in mucosa-associated lymphoid tissue (MALT) lymphoma of different sites. Methods One hundred and ninety-six cases of MALT lymphoma from Cancer Hospital of Fudan University were enrolled into the

  3. 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.

  4. 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.

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

    Science.gov (United States)

    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.

  6. [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.

  7. The differential diagnostic value of morphological changes of follicular dendritic cell meshwork between benign and malignant lymphoid tissues proliferative lesions%滤泡树突细胞网形态变化在淋巴组织增生性良恶性病变鉴别诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    朱梅刚; 丁向东; 冯晓东; 徐炜

    2012-01-01

    ) meshwork between benign and malignant lymphoid proliferation lesions. Method The morphologic analysis and type of follucular dendritic cell ( FDC ) meshwork was studied by EnVision two-step methods in 60 cases of reactive lymphoid hyperplasia, 5 cases of HV-CD, 3 cases of atypical hyperplasia of T zone, and 78 cases of various lymphomas ( 73 cases of non-Hodgkin lymphoma and 5 cases of Hodgkin lymphoma ). A panel of antibodies used in the benign and malignant lymphoid hyperplasia lesions plus CD21/CD35 were used to label FDC meshwork. Results The reactive hyperplastic lesions showed ball form and regulated meshwork which has intact surface. The HV-CD showed single or multiple ball meshwork or distinct snake-like meshwork. The T zone atypical hyperplasia, early MCL and MZL showed surface invasive meshwork. The diffuse infiltrative MCL, MZL, T zone lymphoma and DLBCL non-GCB showed coloniza-tive meshwork. The DLBCL GCB and diffuse MCL showed burst meshwork. The FL, NLPHL, NLRCHL and NSCHL showed proliferative meshwork. The AITL showed specific extrafollicular around vessel proliferative meshwork. Conclusion All observed results suggest the morphologic changes of FDC meshwork between benign and malignant lymphoid proliferative lesions showed obvious difference. The morphologic changes of FDC meshwork combined with the histopathology, immunohistochemistry and molecular genetic detection may helpful for the differential diagnosis between benign and malignant of lymphoid proliferative lesions.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. phMRI: methodological considerations for mitigating potential confounding factors

    Directory of Open Access Journals (Sweden)

    Julius H Bourke

    2015-05-01

    Full Text Available Pharmacological Magnetic Resonance Imaging (phMRI is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g. clinical neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome.

  14. Negative confounding by essential fatty acids in methylmercury neurotoxicity associations

    DEFF Research Database (Denmark)

    Choi, Anna L; Mogensen, Ulla Brasch; Bjerve, Kristian S

    2014-01-01

    acid concentrations in the analysis (-22.0, 95% confidence interval [CI]=-39.4, -4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after...... concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder......-adjusted associations with methylmercury exposure. RESULTS: A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (-18.9, 95% confidence interval [CI]=-36.3, -1.51). The association became stronger after the inclusion of fatty...

  15. Saccade-confounded image statistics explain visual crowding.

    Science.gov (United States)

    Nandy, Anirvan S; Tjan, Bosco S

    2012-01-08

    Processing of shape information in human peripheral visual fields is impeded beyond what can be expected by poor spatial resolution. Visual crowding, the inability to identify objects in clutter, has been shown to be the primary factor limiting shape perception in peripheral vision. Despite the well-documented effects of crowding, its underlying causes remain poorly understood. Given that spatial attention both facilitates learning of image statistics and directs saccadic eye movements, we propose that the acquisition of image statistics in peripheral visual fields is confounded by eye-movement artifacts. Specifically, the image statistics acquired under a peripherally deployed spotlight of attention are systematically biased by saccade-induced image displacements. These erroneously represented image statistics lead to inappropriate contextual interactions in the periphery and cause crowding.

  16. Quality of reporting of confounding remained suboptimal after the STROBE guideline

    NARCIS (Netherlands)

    Pouwels, Koen B; Widyakusuma, Niken N; Groenwold, Rolf Hh; Hak, Eelko

    Objectives: Poor quality of reporting of confounding has been observed in observational studies prior the STrenghtening the Reporting of Observational studies in Epidemiology (STROBE) statement, a reporting guideline for observational studies. We assessed whether the reporting of confounding

  17. Quality of reporting of confounding remained suboptimal after the STROBE guideline

    NARCIS (Netherlands)

    Pouwels, Koen B.; Widyakusuma, Niken N.; Groenwold, Rolf H H|info:eu-repo/dai/nl/30481203X; Hak, Eelko

    2016-01-01

    Objectives Poor quality of reporting of confounding has been observed in observational studies prior the STrenghtening the Reporting of Observational studies in Epidemiology (STROBE) statement, a reporting guideline for observational studies. We assessed whether the reporting of confounding improved

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    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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  2. 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

  3. 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.

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

    Science.gov (United States)

    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.

  5. 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

  6. 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...

  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. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Determining Confounding Sensitivities In Eddy Current Thin Film Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

    2016-07-01

    Determining Confounding Sensitivities In Eddy Current Thin Film Measurements Ethan Gros, Lalita Udpa, Electrical Engineering, Michigan State University, East Lansing MI 48824 James A. Smith, Experiment Analysis, Idaho National Laboratory, Idaho Falls ID 83415 Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It is the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy current testing is performed using a commercially available, hand held eddy current probe (ETA3.3H spring loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe is sent to a hand held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring

  14. 黏膜相关淋巴样组织淋巴瘤易位蛋白功能及其在血液肿瘤中对核因子-κB信号通路的调节作用%Function of mucosa-associated lymphoid tissue lymphoma translocation protein 1 and its regulation of nuclear factor-κB signaling pathway in hematologic neoplasms

    Institute of Scientific and Technical Information of China (English)

    罗建萍; 李振宇

    2016-01-01

    Mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) 1 is a key regulator of antigen-induced nuclear factor-κB activation in the adaptive immune response.Activation of proteolytic activity of the MALT1 is shown to boost the immune response.Recent studies have shown that MALT1 proteolytic activity was essential for the survival and proliferation of cells of MALT1-dependent lymphoma,such as activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL) and MALT lymphoma.It was also reported to be associated with the development of T cell acute lymphoblastic leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL),and it was overexpressed in myeloma cell lines.This article reviews literatures on the function of MALT1 and its regulation of nuclear factor-κB signaling pathway.%在机体适应性免疫反应中,黏膜相关淋巴样组织淋巴瘤易位蛋白(MALT)1是抗原诱导的核因子-κB信号通路激活的关键因子,其蛋白酶活性的激活可增强机体免疫反应.近年来,相关研究结果表明,MALT1的蛋白酶活性对MALT1依赖性淋巴瘤[活化B细胞样亚型弥漫大B细胞淋巴瘤(ABC-DLBCL)与MALT淋巴瘤]细胞生存及增殖是必需的;亦有文献报道,MALT1与急性T淋巴细胞白血病(T-ALL)、急性B淋巴细胞白血病(B-ALL)的发生相关,且在骨髓瘤细胞株中过表达.笔者拟就MALT1的功能、对核因子-κB信号通路的调节作用及其与血液系统肿瘤的关系进行综述.

  15. 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.

  16. Heterogeneity Confounds Establishment of "a" Model Microbial Strain.

    Science.gov (United States)

    Keller, Nancy P

    2017-02-21

    Aspergillus fumigatus is a ubiquitous environmental mold and the leading cause of diverse human diseases ranging from allergenic bronchopulmonary aspergillosis (ABPA) to invasive pulmonary aspergillosis (IPA). Experimental investigations of the biology and virulence of this opportunistic pathogen have historically used a few type strains; however, it is increasingly observed with this fungus that heterogeneity among isolates potentially confounds the use of these reference isolates. Illustrating this point, Kowalski et al. (mBio 7:e01515-16, 2016, https://doi.org/10.1128/mBio.01515-16) demonstrated that variation in 16 environmental and clinical isolates of A. fumigatus correlated virulence with fitness in low oxygen, whereas Fuller et al. (mBio 7:e01517-16, 2016, https://doi.org/10.1128/mBio.01517-16) showed wide variation in light responses at a physiological and protein functionality level in 15 A. fumigatus isolates. In both studies, two commonly used type strains, Af293 and CEA10, displayed significant differences in physiological responses to abiotic stimuli and virulence in a murine model of IPA.

  17. Confounding Impacts of Iron Reduction on Arsenic Retention

    Energy Technology Data Exchange (ETDEWEB)

    Tufano, K.J.; Fendorf, S.

    2009-05-26

    A transition from oxidizing to reducing conditions has long been implicated to increase aqueous As concentrations, for which reductive dissolution of iron (hydr)oxides is commonly implicated as the primary culprit. Confounding our understanding of processes controlling As retention, however, is that reductive transformation of ferrihydrite has recently been shown to promote As retention rather than release. To resolve the role iron phases have in regulating arsenic concentrations, here we examine As desorption from ferrihydrite-coated sands presorbed with As(lll); experiments were performed at circumneutral pH under Fe-reducing conditions with the dissimilatory iron reducing bacterium Shewanella putrefaciens strain CN-32 over extended time periods. We reveal that with the initial phase of iron reduction, ferrihydrite undergoes transformation to secondary phases and increases As(lll) retention (relative to abiotic controls). However, with increased reaction time, cessation of the phase transitions and ensuing reductive dissolution result in prolonged release of As(III) to the aqueous phase. Our results suggest that As(lll) retention during iron reduction is temporally dependent on secondary precipitation of iron phases; during transformation to secondary phases, particularly magnetite, As(lll) retention is enhanced even relative to oxidized systems. However, conditions that retard secondary transformation (more stable iron oxides or limited iron reducing bacterial activity), or prolonged anaerobiosis, will lead to both the dissolution of ferric (hydr)oxides and release of As(lll) to the aqueous phase.

  18. Diagnostic and therapeutic strategy for confounding radiation myelitis.

    Science.gov (United States)

    Higashida, Tetsuhiro; Colen, Chaim B; Guthikonda, Murali

    2010-05-01

    We report a case of confounding radiation myelitis to demonstrate the usefulness of surgical biopsy in ensuring the correct diagnosis and to avoid unnecessary treatment. The patient was a 40-year-old man with a history of epiglottis carcinoma and sarcoidosis. Six months after radiation therapy and chemotherapy for epiglottis carcinoma, he noticed paresthesia and dysesthesia in the left arm and leg. Two months after that, he complained of severe neck pain and rapidly progressing weakness in all extremities. MRI showed an enhanced intramedullary lesion with extensive edema in the cervical spinal cord. Radiation myelitis, intramedullary spinal tumor, and neurosarcoidosis were considered as differential diagnoses. Spinal cord biopsy with laminectomy was performed and radiation myelitis was diagnosed. After the surgery, the lesion was significantly decreased in size even though corticosteroid therapy was rapidly tapered. We emphasize that a spinal cord biopsy is indicated to obtain a pathological diagnosis and to make a clear treatment strategy for patients with associated diseases causing lesions of the spinal cord.

  19. TISSUE-Tregs

    Science.gov (United States)

    Panduro, Marisella; Benoist, Christophe; Mathis, Diane

    2016-01-01

    The immune system is responsible for defending an organism against the myriad of microbial invaders it constantly confronts. It has become increasingly clear that the immune system has a second major function: the maintenance of organismal homeostasis. Foxp3+CD4+ regulatory T cells (Tregs) are important contributors to both of these critical activities, defense being the primary purview of Tregs circulating through lymphoid organs, and homeostasis ensured mainly by their counterparts residing in parenchymal tissues. This review focuses on so-called tissue Tregs. We first survey existing information on the phenotype, function, sustaining factors, and human equivalents of the three best-characterized tissue-Treg populations—those operating in visceral adipose tissue, skeletal muscle, and the colonic lamina propria. We then attempt to distill general principles from this body of work—as concerns the provenance, local adaptation, molecular sustenance, and targets of action of tissue Tregs, in particular. PMID:27168246

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. 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.

  8. 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.

  9. 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 ...

  10. 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.

  11. 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.

  12. 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.

  13. Handling stress may confound murine gut microbiota studies

    Directory of Open Access Journals (Sweden)

    Cary R. Allen-Blevins

    2017-01-01

    Full Text Available Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO, the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis, a species sensitive to host stress (Bailey & Coe, 2004. Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS solution or deionized, distilled water. Gastrointestinal (GI tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and

  14. Handling stress may confound murine gut microbiota studies

    Science.gov (United States)

    Allen-Blevins, Cary R.; You, Xiaomeng; Hinde, Katie

    2017-01-01

    Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis), a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and Firmicutes

  15. Determining confounding sensitivities in eddy current thin film measurements

    Science.gov (United States)

    Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

    2017-02-01

    Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done by using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It was the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy-current testing was performed using a commercially available, hand-held eddy-current probe (ETA3.3H spring-loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe was sent to a hand-held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring-loaded eddy probe was at measuring film thickness under varying experimental conditions. This research studied the effects of a number of factors such as i) conductivity, ii) edge effect, iii) surface finish of base material and iv) cable condition.

  16. Handling stress may confound murine gut microbiota studies.

    Science.gov (United States)

    Allen-Blevins, Cary R; You, Xiaomeng; Hinde, Katie; Sela, David A

    2017-01-01

    Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis), a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and Firmicutes. Our results demonstrate

  17. From bad to worse: collider stratification amplifies confounding bias in the "obesity paradox".

    Science.gov (United States)

    Banack, Hailey R; Kaufman, Jay S

    2015-10-01

    Smoking is often identified as a confounder of the obesity-mortality relationship. Selection bias can amplify the magnitude of an existing confounding bias. The objective of the present report is to demonstrate how confounding bias due to cigarette smoking is increased in the presence of collider stratification bias using an empirical example and directed acyclic graphs. The empirical example uses data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of 15,792 men and women in the United States. Poisson regression models were used to examine the confounding effect of smoking. In the total ARIC study population, smoking produced a confounding bias of confounding bias induced by smoking is greater in the presence of collider stratification bias.

  18. [Genetic bases of diversity of the repertoire of immunoglobulins in application to diagnostics of clonality of B-cell lymphoid populations].

    Science.gov (United States)

    Zakharova, E S; Kazilo, N A; Stefanov, D N; Sinitsina, M N; Kovrigina, A M

    2011-06-01

    Molecular mechanisms underlying the formation of B-cell lymphomas in connection with processes associated with the maturation of B lymphocytes are reviewed. The currently used diagnostic methods do not always distinguish lymphomas from reactive changes of the lymphoid tissue. The principle of the molecular genetic method ofclonality detection in lymphocyte populations, technical problems, and the strategy of its application in clinical diagnostics of lymphomas are described in detail.

  19. Control of confounding in the analysis phase – an overview for clinicians

    Science.gov (United States)

    Kahlert, Johnny; Gribsholt, Sigrid Bjerge; Gammelager, Henrik; Dekkers, Olaf M; Luta, George

    2017-01-01

    In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residual confounding and suffer from the difficulty of identifying true confounders. Even in large health care databases, insufficient or poor data may contribute to these challenges. The trend in data collection is to compile more fine-grained data on lifestyle and severity of diseases, based on self-reporting and modern technologies. This will surely improve our ability to incorporate relevant confounders or their proxies. However, despite a remarkable development of methods that account for confounding and new data opportunities, confounding will remain a serious issue. Considering the advantages and

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. On the role of marginal confounder prevalence - implications for the high-dimensional propensity score algorithm.

    Science.gov (United States)

    Schuster, Tibor; Pang, Menglan; Platt, Robert W

    2015-09-01

    The high-dimensional propensity score algorithm attempts to improve control of confounding in typical treatment effect studies in pharmacoepidemiology and is increasingly being used for the analysis of large administrative databases. Within this multi-step variable selection algorithm, the marginal prevalence of non-zero covariate values is considered to be an indicator for a count variable's potential confounding impact. We investigate the role of the marginal prevalence of confounder variables on potentially caused bias magnitudes when estimating risk ratios in point exposure studies with binary outcomes. We apply the law of total probability in conjunction with an established bias formula to derive and illustrate relative bias boundaries with respect to marginal confounder prevalence. We show that maximum possible bias magnitudes can occur at any marginal prevalence level of a binary confounder variable. In particular, we demonstrate that, in case of rare or very common exposures, low and high prevalent confounder variables can still have large confounding impact on estimated risk ratios. Covariate pre-selection by prevalence may lead to sub-optimal confounder sampling within the high-dimensional propensity score algorithm. While we believe that the high-dimensional propensity score has important benefits in large-scale pharmacoepidemiologic studies, we recommend omitting the prevalence-based empirical identification of candidate covariates. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Quality of reporting of confounding remained suboptimal after the STROBE guideline

    NARCIS (Netherlands)

    Pouwels, Koen B; Widyakusuma, Niken N; Groenwold, Rolf Hh; Hak, Eelko

    2016-01-01

    OBJECTIVES: Poor quality of reporting of confounding has been observed in observational studies prior the STROBE statement, a reporting guideline for observational studies. We assessed whether the reporting of confounding improved after the STROBE statement. STUDY DESIGN AND SETTING: We searched Med

  6. Quantitative assessment of unobserved confounding is mandatory in nonrandomized intervention studies

    NARCIS (Netherlands)

    Groenwold, R H H; Hak, E; Hoes, A W

    2009-01-01

    OBJECTIVE: In nonrandomized intervention studies unequal distribution of patient characteristics in the groups under study may hinder comparability of prognosis and therefore lead to confounding bias. Our objective was to review methods to control for observed confounding, as well as unobserved conf

  7. Confounding by dietary pattern of the inverse association between alcohol consumption and type 2 diabetes risk

    Science.gov (United States)

    Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as ...

  8. Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk

    Science.gov (United States)

    Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome this limitation. To examine confounding by dietary pattern as well as ...

  9. Bed Sharing, SIDS Research, and the Concept of Confounding: A Review for Public Health Nurses.

    Science.gov (United States)

    Keys, Elizabeth M; Rankin, James A

    2015-01-01

    Confounding is an important concept for public health nurses (PHNs) to understand when considering the results of epidemiological research. The term confounding is derived from Latin, confundere, which means to "mix-up" or "mix together". Epidemiologists attempt to derive a cause and effect relationship between two variables traditionally known as the exposure and disease (e.g., smoking and lung cancer). Confounding occurs when a third factor, known as a confounder, leads to an over- or underestimate of the magnitude of the association between the exposure and disease. An understanding of confounding will facilitate critical appraisal of epidemiological research findings. This knowledge will enable PHNs to strengthen their evidence-based practice and better prepare them for policy development and implementation. In recent years, researchers and clinicians have examined the relationship between bed sharing and sudden infant death syndrome (SIDS). The discussion regarding the risk of bed sharing and SIDS provides ample opportunity to discuss the various aspects of confounding. The purpose of this article is to use the bed sharing and SIDS literature to assist PHNs to understand confounding and to apply this knowledge when appraising epidemiological research. In addition, strategies that are used to control confounding are discussed.

  10. Structural confounding of area-level deprivation and segreation: an empirical example

    Science.gov (United States)

    The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood.

    Science.gov (United States)

    Hamilton, Carly A; Mahan, Suman; Bell, Charlotte R; Villarreal-Ramos, Bernardo; Charleston, Bryan; Entrican, Gary; Hope, Jayne C

    2017-05-01

    Natural killer (NK) cells are widely distributed in lymphoid and non-lymphoid tissues, but little is known about the recirculation of NK cells between blood and tissues. This is relevant to understanding recirculation in the steady-state and also for determining the roles for NK cells in vaccine-induced immunity and responses to infection. Therefore, the percentage of NK cells and their phenotype across peripheral blood, afferent lymph and lymph nodes in steady-state conditions was investigated in cattle using the pseudo-afferent lymphatic cannulation model. CD2(+) CD25(lo) NK cells were the predominant subset of NK cells within the blood. In contrast, CD2(-) CD25(hi) NK cells were the main subset present within the skin-draining afferent lymphatic vessels and lymph nodes, indicating that CD2(-) NK cells are the principal NK cell subset trafficking to lymph nodes via the afferent lymphatic vessel. Furthermore, a low percentage of NK cells were present in efferent lymph, which were predominantly of the CD2(-) subset, indicating that NK cells can egress from lymph nodes and return to circulation in steady-state conditions. These compartmentalization data indicate that NK cells represent a population of recirculating lymphocytes in steady-state conditions and therefore may be important during immune responses to vaccination or infection. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

  16. Systematically missing confounders in individual participant data meta-analysis of observational cohort studies

    DEFF Research Database (Denmark)

    Jackson, D.; White, I.; Kostis, J.B.

    2009-01-01

    One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between...... an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential...... confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease...

  17. Bayesian modeling of cost-effectiveness studies with unmeasured confounding: a simulation study.

    Science.gov (United States)

    Stamey, James D; Beavers, Daniel P; Faries, Douglas; Price, Karen L; Seaman, John W

    2014-01-01

    Unmeasured confounding is a common problem in observational studies. Failing to account for unmeasured confounding can result in biased point estimators and poor performance of hypothesis tests and interval estimators. We provide examples of the impacts of unmeasured confounding on cost-effectiveness analyses using observational data along with a Bayesian approach to correct estimation. Assuming validation data are available, we propose a Bayesian approach to correct cost-effectiveness studies for unmeasured confounding. We consider the cases where both cost and effectiveness are assumed to have a normal distribution and when costs are gamma distributed and effectiveness is normally distributed. Simulation studies were conducted to determine the impact of ignoring the unmeasured confounder and to determine the size of the validation data required to obtain valid inferences.

  18. Knockdown of lymphoid enhancer factor 1 inhibits colon cancer progression in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Wen-Juan Wang

    Full Text Available Expression of lymphoid enhancer factor 1 (LEF1 is frequently altered in different human cancers. This study aimed to assess LEF1 expression in colon cancer tissues and to explore changed phenotypes, gene expressions, and the possible mechanism after knocked down LEF1 expression in colon cancer cell lines. A total of 106 colon cancer and matched paratumorous normal tissues were used to assess LEF1 expression using immunohistochemistry and qRT-PCR. LEF1 lentivirus was used to knockdown LEF1 expression for the assessment of cell viability, cell cycle distribution, apoptosis, and gene expressions. The nude mouse xenograft assay was performed to detect the effects of LEF1 knockdown in vivo. The data showed that the levels of LEF1 mRNA and protein were significantly increased in human colon cancer tissues compared to the matched paratumorous normal tissues and were associated with infiltration depth, lymph node and distant metastases, advanced TNM (tumor-node-metastasis stages, and shorter overall survival. Furthermore, LEF1 knockdown reduced tumor cell viability, invasion capacity, MMP2 and MMP-9 expression, but induced apoptosis. Nude mouse xenograft assay showed that LEF1 knockdown suppressed tumor formation and growth in vivo. In addition, the expression of Notch pathway-related proteins RBP-jκ and Hes1 was reduced in LEF1 knockdown cells. Taken together, LEF1 protein was overexpressed in colon cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in vitro and in vivo. These data suggest that targeting of LEF1 expression should be further evaluated for colon cancer prevention and therapy.

  19. Knockdown of lymphoid enhancer factor 1 inhibits colon cancer progression in vitro and in vivo.

    Science.gov (United States)

    Wang, Wen-Juan; Yao, Yu; Jiang, Li-Li; Hu, Ting-Hua; Ma, Jie-Qun; Liao, Zi-Jun; Yao, Jun-Tao; Li, Dong-Fan; Wang, Shu-Hong; Nan, Ke-Jun

    2013-01-01

    Expression of lymphoid enhancer factor 1 (LEF1) is frequently altered in different human cancers. This study aimed to assess LEF1 expression in colon cancer tissues and to explore changed phenotypes, gene expressions, and the possible mechanism after knocked down LEF1 expression in colon cancer cell lines. A total of 106 colon cancer and matched paratumorous normal tissues were used to assess LEF1 expression using immunohistochemistry and qRT-PCR. LEF1 lentivirus was used to knockdown LEF1 expression for the assessment of cell viability, cell cycle distribution, apoptosis, and gene expressions. The nude mouse xenograft assay was performed to detect the effects of LEF1 knockdown in vivo. The data showed that the levels of LEF1 mRNA and protein were significantly increased in human colon cancer tissues compared to the matched paratumorous normal tissues and were associated with infiltration depth, lymph node and distant metastases, advanced TNM (tumor-node-metastasis) stages, and shorter overall survival. Furthermore, LEF1 knockdown reduced tumor cell viability, invasion capacity, MMP2 and MMP-9 expression, but induced apoptosis. Nude mouse xenograft assay showed that LEF1 knockdown suppressed tumor formation and growth in vivo. In addition, the expression of Notch pathway-related proteins RBP-jκ and Hes1 was reduced in LEF1 knockdown cells. Taken together, LEF1 protein was overexpressed in colon cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in vitro and in vivo. These data suggest that targeting of LEF1 expression should be further evaluated for colon cancer prevention and therapy.

  20. 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