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Sample records for lymphoid progenitors clps

  1. Fetal Lymphoid Progenitors Become Restricted to B-1 Fates Coincident with IL-7Rα Expression.

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    Ryuji Iida

    Full Text Available B-1 cells represent a sub-fraction of B lymphocytes that participate in T cell-independent antibody production and contribute to innate immunity. While the production of B-1 cells is favored during the fetal waves of lymphopoiesis, it has been unclear when and how that differentiation option is specified. To clarify this, lymphoid and hematopoietic progenitors of fetal liver (FL and adult bone marrow (ABM were examined for the B cell differentiation potential. Mouse common lymphoid progenitors (CLPs and more primitive KSL fraction of FL and ABM were transferred to SCID mice and donor-derived B cell subsets were analyzed 4 weeks later. CLPs were also cultured on ST2 stromal cells for 6 days prior to transplantation. While Lin- IL-7Rα+ CLPs from ABM differentiated to B-1, B-2 and marginal zone B (MZB cells, equivalent cells from d15 FL differentiated mostly to B-1a cells. We found that fetal CLPs had less ability to colonize the bone marrow than adult CLPs. However, the fetal/adult difference was already present when progenitors were cultured in an identical condition before transplantation. More primitive KSL fraction of FL could generate the same broad spectrum of B cells typical of adults, including splenic MZB cells. In conclusion, we argue that FL and ABM-CLPs are intrinsically different regarding B-1/B-2 fates and the difference is acquired just before or coincident with the acquisition of IL-7Rα expression.

  2. Common-Lymphoid-Progenitor-Independent Pathways of Innate and T Lymphocyte Development

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    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.

  3. Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

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    Horton, Sarah J; Giotopoulos, George; Yun, Haiyang; Vohra, Shabana; Sheppard, Olivia; Bashford-Rogers, Rachael; Rashid, Mamunur; Clipson, Alexandra; Chan, Wai-In; Sasca, Daniel; Yiangou, Loukia; Osaki, Hikari; Basheer, Faisal; Gallipoli, Paolo; Burrows, Natalie; Erdem, Ayşegül; Sybirna, Anastasiya; Foerster, Sarah; Zhao, Wanfeng; Sustic, Tonci; Petrunkina Harrison, Anna; Laurenti, Elisa; Okosun, Jessica; Hodson, Daniel; Wright, Penny; Smith, Ken G; Maxwell, Patrick; Fitzgibbon, Jude; Du, Ming Q; Adams, David J; Huntly, Brian J P

    2017-09-01

    Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies.

  4. Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging.

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    Young, Kira; Borikar, Sneha; Bell, Rebecca; Kuffler, Lauren; Philip, Vivek; Trowbridge, Jennifer J

    2016-10-17

    Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of changes with age in the heterogeneous multipotent progenitor (MPP) cell compartment, which is long lived and responsible for dynamically regulating output of mature hematopoietic cells. In this study, we observe an early and progressive loss of lymphoid-primed MPP cells (LMPP/MPP4) with aging, concomitant with expansion of HSCs. Transcriptome and in vitro functional analyses at the single-cell level reveal a concurrent increase in cycling of aging LMPP/MPP4 with loss of lymphoid priming and differentiation potential. Impaired lymphoid differentiation potential of aged LMPP/MPP4 is not rescued by transplantation into a young bone marrow microenvironment, demonstrating cell-autonomous changes in the MPP compartment with aging. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging. © 2016 Young et al.

  5. Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

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    Kikushige, Yoshikane; Miyamoto, Toshihiro

    2015-11-01

    Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

  6. Global transcriptome analysis of T-competent progenitors in the bone marrow

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    Vionnie W.C. Yu

    2015-09-01

    Full Text Available T cells are known to develop in the thymus. However, molecular events that control the transition from hematopoietic progenitor cells in the bone marrow to T precursor cells seeded in the thymus remained poorly defined. Our recent report showed that osteocalcin (Ocn-expressing bone cells in the bone marrow have major impact on T cell immunity by regulating T progenitor development in the bone marrow (Yu et al., 2015 [1]. Selective endogenous depletion of Ocn+ cells by inducible diphtheria toxin receptor expression (OcnCre;iDTR led to reduction of T-competent common lymphoid progenitors (Ly6D− CLPs in the bone marrow and loss of T cells in the thymus. Expression of the Notch ligand DLL4 by Ocn+ cells in the bone marrow ensures the production of Ly6D− CLPs, and expression of chemotactic molecules CCR7 and PSGL1 to enable subsequent thymic seeding. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell based adaptive immunity. Here we present the transcriptome profiles of Ly6D− CLPs derived from Ocn+ cells deleted mice (OcnCre+;iDTR compared to those derived from control littermates (OcnCre−;iDTR. These data are publically available from NCBI Gene Expression Omnibus (GEO with the accession number GSE66102.

  7. Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells.

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    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

  8. Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

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    Jessica Purizaca

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

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

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

    2016-01-01

    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...

  10. Comparative study of hematopoietic stem and progenitor cells between sexes in mice under physiological conditions along time.

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    Gasco, Samanta; Rando, Amaya; Zaragoza, Pilar; García-Redondo, Alberto; Calvo, Ana Cristina; Osta, Rosario

    2017-12-01

    Hematopoietic stem and progenitor cells (HSPCs) are attractive targets in regenerative medicine, although the differences in their homeostatic maintenance between sexes along time are still under debate. We accurately monitored hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs) frequencies by flow cytometry, by performing serial peripheral blood extractions from male and female B6SJL wild-type mice and found no significant differences. Only modest differences were found in the gene expression profile of Slamf1 and Gata2. Our findings suggest that both sexes could be used indistinctly to perform descriptive studies in the murine hematopoietic system, especially for flow cytometry studies in peripheral blood. This would allow diminishing the number of animals needed for the experimental procedures. In addition, the use of serial extractions in the same animals drastically decreases the number of animals needed. © 2017 International Federation for Cell Biology.

  11. Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors.

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    Mega, Tiziana; Lupia, Michela; Amodio, Nicola; Horton, Sarah J; Mesuraca, Maria; Pelaggi, Daniela; Agosti, Valter; Grieco, Michele; Chiarella, Emanuela; Spina, Raffaella; Moore, Malcolm A S; Schuringa, Jan Jacob; Bond, Heather M; Morrone, Giovanni

    2011-07-01

    Zinc finger protein 521 (EHZF/ZNF521) is a multi-functional transcription co-factor containing 30 zinc fingers and an amino-terminal motif that binds to the nucleosome remodelling and histone deacetylase (NuRD) complex. ZNF521 is believed to be a relevant player in the regulation of the homeostasis of the hematopoietic stem/progenitor cell compartment, however the underlying molecular mechanisms are still largely unknown. Here, we show that this protein plays an important role in the control of B-cell development by inhibiting the activity of early B-cell factor-1 (EBF1), a master factor in B-lineage specification. In particular, our data demonstrate that: (1) ZNF521 binds to EBF1 via its carboxyl-terminal portion and this interaction is required for EBF1 inhibition; (2) NuRD complex recruitment by ZNF521 is not essential for the inhibition of transactivation of EBF1-dependent promoters; (3) ZNF521 represses EBF1 target genes in a human B-lymphoid molecular context; and (4) RNAi-mediated silencing of ZNF521/Zfp521 in primary human and murine hematopoietic progenitors strongly enhances the generation of B-lymphocytes in vitro. Taken together, our data indicate that ZNF521 can antagonize B-cell development and lend support to the notion that it may contribute to conserve the multipotency of primitive lympho-myeloid progenitors by preventing or delaying their EBF1-driven commitment toward the B-cell lineage.

  12. Human CD5+ Innate Lymphoid Cells Are Functionally Immature and Their Development from CD34+ Progenitor Cells Is Regulated by Id2

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    Maho Nagasawa

    2017-08-01

    Full Text Available Innate lymphoid cells (ILCs have emerged as a key cell type involved in surveillance and maintenance of mucosal tissues. Mouse ILCs rely on the transcriptional regulator Inhibitor of DNA-binding protein 2 (Id2 for their development. Here, we show that Id2 also drives development of human ILC because forced expression of Id2 in human thymic progenitors blocked T cell commitment, upregulated CD161 and promyelocytic leukemia zinc finger (PLZF, and maintained CD127 expression, markers that are characteristic for human ILCs. Surprisingly CD5 was also expressed on these in vitro generated ILCs. This was not an in vitro artifact because CD5 was also found on ex vivo isolated ILCs from thymus and from umbilical cord blood. CD5 was also expressed on small proportions of ILC2 and ILC3. CD5+ ILCs were functionally immature, but could further differentiate into mature CD5− cytokine-secreting ILCs. Our data show that Id2 governs human ILC development from thymic progenitor cells toward immature CD5+ ILCs.

  13. Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice

    International Nuclear Information System (INIS)

    Zhang, Yandong; Yu, Xinchun; Sun, Shuhui; Li, Qian; Xie, Yunli; Li, Qiang; Zhao, Yifan; Pei, Jianfeng; Zhang, Wenmin; Xue, Peng; Zhou, Zhijun; Zhang, Yubin

    2016-01-01

    The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3 months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells. In accordance with increased myeloid progenitors and decreased lymphoid progenitors, the BM and spleens of Cd-treated mice had more monocytes and/or neutrophils and fewer B cells and T cells. Cd impaired the ability of the non-hematopoietic system to support LT-HSCs, in that lethally irradiated Cd-treated recipients transplanted with normal BM cells had reduced LT-HSCs after the hematopoietic system was fully reconstituted. This is consistent with reduced osteoblasts, a known critical component for HSC niche, observed in Cd-treated mice. Conversely, lethally irradiated control recipients transplanted with BM cells from Cd-treated mice had normal LT-HSC reconstitution. Furthermore, both control mice and Cd-treated mice that received Alendronate, a clinical drug used for treating osteoporosis, had BM increases of LT-HSCs. Thus, the results suggest Cd increase of LT-HSCs is due to effects on HSCs and not on osteoblasts, although, Cd causes osteoblast reduction and impaired niche function for maintaining HSCs. Furthermore, Cd skews HSCs toward myelopoiesis. - Highlights: • Cd increases the number of LT-HSCs but impairs their development. • Cd-treated hosts have compromised ability to support LT-HSCs. • Cd promotes myelopoiesis at the expense of lymphopoiesis at the MPP level.

  14. Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice

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    Zhang, Yandong; Yu, Xinchun [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Li, Qian [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China); Xie, Yunli [Insititute of Brain Sciences, Fudan University, Shanghai 200032 (China); Li, Qiang [Putuo District Center for Disease Control and Prevention, Shanghai 200062 (China); Zhao, Yifan; Pei, Jianfeng; Zhang, Wenmin; Xue, Peng; Zhou, Zhijun [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China); Zhang, Yubin, E-mail: yz001@fudan.edu.cn [School of Public Health and Key Laboratory of Public Health, MOE, Fudan University, Shanghai 200032 (China)

    2016-12-15

    The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3 months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells. In accordance with increased myeloid progenitors and decreased lymphoid progenitors, the BM and spleens of Cd-treated mice had more monocytes and/or neutrophils and fewer B cells and T cells. Cd impaired the ability of the non-hematopoietic system to support LT-HSCs, in that lethally irradiated Cd-treated recipients transplanted with normal BM cells had reduced LT-HSCs after the hematopoietic system was fully reconstituted. This is consistent with reduced osteoblasts, a known critical component for HSC niche, observed in Cd-treated mice. Conversely, lethally irradiated control recipients transplanted with BM cells from Cd-treated mice had normal LT-HSC reconstitution. Furthermore, both control mice and Cd-treated mice that received Alendronate, a clinical drug used for treating osteoporosis, had BM increases of LT-HSCs. Thus, the results suggest Cd increase of LT-HSCs is due to effects on HSCs and not on osteoblasts, although, Cd causes osteoblast reduction and impaired niche function for maintaining HSCs. Furthermore, Cd skews HSCs toward myelopoiesis. - Highlights: • Cd increases the number of LT-HSCs but impairs their development. • Cd-treated hosts have compromised ability to support LT-HSCs. • Cd promotes myelopoiesis at the expense of lymphopoiesis at the MPP level.

  15. TOX sets the stage for innate lymphoid cells

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    Spits, Hergen

    2015-01-01

    Like T cells and B cells, innate lymphoid cells (ILCs) develop from common lymphoid progenitors, but how commitment to the ILC lineage is regulated has remained unclear. The transcriptional regulator TOX is important in this process

  16. Deciphering the Innate Lymphoid Cell Transcriptional Program

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    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.

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

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    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. Copyright © 2016 by The American Association of Immunologists, Inc.

  18. Innate lymphoid cells in secondary lymphoid organs.

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    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. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Human innate lymphoid cells

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Spits, Hergen

    2014-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of

  20. Total lymphoid irradiation

    International Nuclear Information System (INIS)

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

    1983-01-01

    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

  1. Characteristic of innate lymphoid cells (ILC

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    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.

  2. Colonization and effector functions of innate lymphoid cells in mucosal tissues

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    Kim, Myunghoo; Kim, Chang H.

    2016-01-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

  3. Determination of the Fate and Function of Innate Lymphoid Cells Following Adoptive Transfer of Innate Lymphoid Cell Precursors.

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    O'Sullivan, Timothy E; Sun, Joseph C

    2018-01-01

    Innate lymphoid cells are a heterogeneous family of tissue-resident and circulating lymphocytes that play an important role in host immunity. Recent studies have profiled the developmental pathways of mature ILCs and have identified ILC progenitors in the bone marrow through the use of transcription factor reporter mice. Here we describe methodology to identify and isolate bone marrow CHILP and ILC2 progenitor (ILC2P) cells based on cell surface marker expression for adoptive transfer into lymphopenic mice to track the fate of developing ILCs.

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

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    Wei Xu

    2015-03-01

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

  5. Human innate lymphoid cells.

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    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Human innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2016-01-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune

  7. Bioengineering of artificial lymphoid organs

    OpenAIRE

    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 cy...

  8. 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.

  9. 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.

  10. Progenitor Epithelium

    Science.gov (United States)

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134

  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. Why Innate Lymphoid Cells?

    Science.gov (United States)

    Kotas, Maya E; Locksley, Richard M

    2018-06-19

    Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4 + T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense. In this Perspective, we propose mechanisms by which the establishment of ILCs and the tissue lymphoid niche during early development may have consequences much later in life. Although definitive answers require better tools, efforts to achieve deeper understanding of ILC biology across the mammalian lifespan have the potential to lift the veil on the unknown breadth of immune cell functions. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. 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.

  14. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    Science.gov (United States)

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Lymphoid Tissue Grafts in Man

    Energy Technology Data Exchange (ETDEWEB)

    Kay, H. E.M. [Royal Marsden Hospital, Institute of Cancer Research, London (United Kingdom)

    1969-07-15

    Grafts of lymphoid tissue or of lymphoid stem cells may be appropriate in the treatment of some congenital immune deficiency disorders. The reasons for preferring tissues of foetal origin are discussed and the evidence for foetal immunocompetence is briefly summarized. Methods of storing foetal liver cells and cells or fragments of thymus are mentioned, and the organization of the Foetal Tissue Bank of the Royal Marsden Hospital is described. Clinical data from transplantation of lymphoid cells in various immune deficiency disorders are briefly presented. (author)

  16. Colonization and effector functions of innate lymphoid cells in mucosal tissues.

    Science.gov (United States)

    Kim, Myunghoo; Kim, Chang H

    2016-10-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  17. Prions and lymphoid organs

    Science.gov (United States)

    O’Connor, Tracy; Aguzzi, Adriano

    2013-01-01

    Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1−/− lymph nodes and rates of neuroinvasion in TNFR1−/− mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1−/− lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)—the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article. PMID:23357827

  18. Total lymphoid irradiation

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    An outline review notes recent work on total lymphoid irradiation (TLI) as a means of preparing patients for grafts and particularly for bone-marrow transplantation. T.L.I. has proved immunosuppressive in rats, mice, dogs, monkeys and baboons; when given before bone-marrow transplantation, engraftment took place without, or with delayed rejection or graft-versus-host disease. Work with mice has indicated that the thymus needs to be included within the irradiation field, since screening of the thymus reduced skin-graft survival from 50 to 18 days, though irradiation of the thymus alone has proved ineffective. A more lasting tolerance has been observed when T.L.I. is followed by an injection of donor bone marrow. 50% of mice treated in this way accepted allogenic skin grafts for more than 100 days, the animals proving to be stable chimeras with 50% of their peripheral blood lymphocytes being of donor origin. Experiments of a similar nature with dogs and baboons were not so successful. (U.K.)

  19. 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.

  20. Innate lymphoid cells and the skin

    OpenAIRE

    Salimi, Maryam; Ogg, Graham

    2014-01-01

    Innate lymphoid cells are an emerging family of effector cells that contribute to lymphoid organogenesis, metabolism, tissue remodelling and protection against infections. They maintain homeostatic immunity at barrier surfaces such as lung, skin and gut (Nature 464:1367?1371, 2010, Nat Rev Immunol 13: 145?149, 2013). Several human and mouse studies suggest a role for innate lymphoid cells in inflammatory skin conditions including atopic eczema and psoriasis. Here we review the innate lymphoid...

  1. Florid reactive lymphoid hyperplasia of terminal ileum

    OpenAIRE

    Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

    2010-01-01

    Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn’s disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn’s disease. In florid lymphoid hyperplasia limited resection may b...

  2. Activation of the Arterial Program Drives Development of Definitive Hemogenic Endothelium with Lymphoid Potential

    Directory of Open Access Journals (Sweden)

    Mi Ae Park

    2018-05-01

    Full Text Available Summary: Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs arise from hemogenic endothelium (HE lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4. Blood cells generated from arterial HE were more than 100-fold enriched in T cell precursor frequency and possessed the capacity to produce B lymphocytes and red blood cells expressing high levels of BCL11a and β-globin. Together, these findings provide an innovative strategy to aid in the generation of definitive lymphomyeloid progenitors and lymphoid cells from hPSCs for immunotherapy through enhancing arterial programming of HE. : Park et al. find that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhances formation of arterial-type hemogenic endothelium (HE from hPSCs. Blood cells generated from arterial HE are highly enriched in definitive lymphomyeloid progenitors. Keywords: human pluripotent stem cells, hemogenic endothelium, T cells, hematopoietic stem cells, hematopoiesis, ETS1, MAPK/ERK signaling

  3. Artificial engineering of secondary lymphoid organs.

    Science.gov (United States)

    Tan, Jonathan K H; Watanabe, Takeshi

    2010-01-01

    Secondary lymphoid organs such as spleen and lymph nodes are highly organized immune structures essential for the initiation of immune responses. They display distinct B cell and T cell compartments associated with specific stromal follicular dendritic cells and fibroblastic reticular cells, respectively. Interweaved through the parenchyma is a conduit system that distributes small antigens and chemokines directly to B and T cell zones. While most structural aspects between lymph nodes and spleen are common, the entry of lymphocytes, antigen-presenting cells, and antigen into lymphoid tissues is regulated differently, reflecting the specialized functions of each organ in filtering either lymph or blood. The overall organization of lymphoid tissue is vital for effective antigen screening and recognition, and is a feature which artificially constructed lymphoid organoids endeavor to replicate. Synthesis of artificial lymphoid tissues is an emerging field that aims to provide therapeutic application for the treatment of severe infection, cancer, and age-related involution of secondary lymphoid tissues. The development of murine artificial lymphoid tissues has benefited greatly from an understanding of organogenesis of lymphoid organs, which has delineated cellular and molecular elements essential for the recruitment and organization of lymphocytes into lymphoid structures. Here, the field of artificial lymphoid tissue engineering is considered including elements of lymphoid structure and development relevant to organoid synthesis. (c) 2010 Elsevier Inc. All rights reserved.

  4. Innate lymphoid cells and asthma.

    Science.gov (United States)

    Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

    2014-04-01

    Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  5. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  6. Innate lymphoid cells in tissue homeostasis and diseases.

    Science.gov (United States)

    Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

    2017-08-18

    Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

  7. Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

    Science.gov (United States)

    Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

    2008-04-01

    The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

  8. Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors

    Directory of Open Access Journals (Sweden)

    Julie Helft

    2017-07-01

    Full Text Available Conventional dendritic cells (cDCs are thought to descend from a DC precursor downstream of the common myeloid progenitor (CMP. However, a mouse lymphoid-primed multipotent progenitor has been shown to generate cDCs following a DC-specific developmental pathway independent of monocyte and granulocyte poiesis. Similarly, here we show that, in humans, a large fraction of multipotent lymphoid early progenitors (MLPs gives rise to cDCs, in particular the subset known as cDC1, identified by co-expression of DNGR-1 (CLEC9A and CD141 (BDCA-3. Single-cell analysis indicates that over one-third of MLPs have the potential to efficiently generate cDCs. cDC1s generated from CMPs or MLPs do not exhibit differences in transcriptome or phenotype. These results demonstrate an early imprinting of the cDC lineage in human hematopoiesis and highlight the plasticity of developmental pathways giving rise to human DCs.

  9. Shaping Innate Lymphoid Cell Diversity

    Directory of Open Access Journals (Sweden)

    Qiutong Huang

    2017-11-01

    Full Text Available Innate lymphoid cells (ILCs are a key cell type that are enriched at mucosal surfaces and within tissues. Our understanding of these cells is growing rapidly. Paradoxically, these cells play a role in maintaining tissue integrity but they also function as key drivers of allergy and inflammation. We present here the most recent understanding of how genomics has provided significant insight into how ILCs are generated and the enormous heterogeneity present within the canonical subsets. This has allowed the generation of a detailed blueprint for ILCs to become highly sensitive and adaptive sensors of environmental changes and therefore exquisitely equipped to protect immune surfaces.

  10. Innate lymphoid cells in inflammation and immunity

    NARCIS (Netherlands)

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

    2014-01-01

    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

  11. Transcriptional control of innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Bernink, Jochem; Peters, Charlotte; Spits, Hergen

    2012-01-01

    Cells that belong to the family of innate lymphoid cells (ILCs) not only form a first line of defense against invading microbes, but also play essential roles in tissue remodeling and immune pathology. Ror?t+ ILCs, producing the cytokines IL-22 and IL-17, include lymphoid tissue inducer (LTi) cells

  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. Innate Lymphoid Cells in Tumor Immunity.

    Science.gov (United States)

    van Beek, Jasper J P; Martens, Anne W J; Bakdash, Ghaith; de Vries, I Jolanda M

    2016-02-25

    Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.

  14. Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential.

    Science.gov (United States)

    Galat, Yekaterina; Dambaeva, Svetlana; Elcheva, Irina; Khanolkar, Aaruni; Beaman, Kenneth; Iannaccone, Philip M; Galat, Vasiliy

    2017-03-17

    The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification. Thus, it has been shown that variations in cytokine and inhibitory molecule treatments in the first few days of hematopoietic differentiation define primitive versus definitive potential of produced hematopoietic progenitor cells. The majority of current feeder-free, defined systems for hematopoietic induction from pluripotent stem cells include prolonged incubations with various cytokines that make the differentiation process complex and time consuming. We established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. The hemogenic endothelium differentiation was accomplished in an adherent, serum-free culture system by applying CHIR99021. Hemogenic endothelium progenitor cells were isolated on day 5 of differentiation and evaluated for their endothelial, myeloid, and lymphoid potential. Monolayer induction based on GSK3 inhibition, described here, yielded a large number of CD31 + CD34 + hemogenic endothelium cells. When isolated and propagated in adherent conditions, these progenitors gave rise to mature endothelium. When further cocultured with OP9 mouse stromal cells, these progenitors gave rise to various cells of myeloid lineages as well as natural killer lymphoid, T-lymphoid

  15. Innate lymphoid cells and their stromal microenvironments.

    Science.gov (United States)

    Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

    2017-09-01

    In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  16. 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.

  17. Cytokinetics and Regulation of Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lajtha, L. G. [Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (United Kingdom)

    1967-07-15

    Full text: In spite of great differences in the life-span of fully differentiated haemic cells, the cellular kinetics of their production appears to be similar. Recent evidence indicates a common ultimate stem cell for most of the cells in the peripheral blood. The various pathways of differentiation, however, result in transient dividing and differentiating cell populations which differ from each other not only in their specific biochemical processes but also in the manner of control and kinetic pattern of their proliferation. The population best understood is the erythroid progenitor series of cells, primarily because it has the greatest number of experimentally measurable parameters at the present. This will be discussed in detail and comparisons will be made with the myeloid and lymphoid progenitor populations. The fine structure of the bone-marrow stem cell population will be examined in particular, with regard to the suitability or otherwise of the current stem cell models to explain the kinetic pattern of all the peripheral blood elements after perturbations of their steady-state values. Four different assay methods of bone-marrow stem cells have been examined with regard to the kinetic pattern following perturbation of the steady-state system, e.g. by irradiation. Basically, the stem cell assays fall into two categories: those depending on grafting haemopoietic cells into suitably treated recipients, and those in which recovery of the population is allowed in the animal in which the perturbation was produced, without handling the cells. Evidence is accumulating which indicates that in the grafting techniques, a selective loss of stem cells may occur, . especially stem cells in cell cycle, hence in early stages of recovery of the population unduly low numerical values might be noted. In view of this observation, the concept of the colony-forming cell may have to be revised and instead the colony-forming property of the stem cell introduced. (author)

  18. Cytokinetics and Regulation of Progenitor Cells

    International Nuclear Information System (INIS)

    Lajtha, L.G.

    1967-01-01

    Full text: In spite of great differences in the life-span of fully differentiated haemic cells, the cellular kinetics of their production appears to be similar. Recent evidence indicates a common ultimate stem cell for most of the cells in the peripheral blood. The various pathways of differentiation, however, result in transient dividing and differentiating cell populations which differ from each other not only in their specific biochemical processes but also in the manner of control and kinetic pattern of their proliferation. The population best understood is the erythroid progenitor series of cells, primarily because it has the greatest number of experimentally measurable parameters at the present. This will be discussed in detail and comparisons will be made with the myeloid and lymphoid progenitor populations. The fine structure of the bone-marrow stem cell population will be examined in particular, with regard to the suitability or otherwise of the current stem cell models to explain the kinetic pattern of all the peripheral blood elements after perturbations of their steady-state values. Four different assay methods of bone-marrow stem cells have been examined with regard to the kinetic pattern following perturbation of the steady-state system, e.g. by irradiation. Basically, the stem cell assays fall into two categories: those depending on grafting haemopoietic cells into suitably treated recipients, and those in which recovery of the population is allowed in the animal in which the perturbation was produced, without handling the cells. Evidence is accumulating which indicates that in the grafting techniques, a selective loss of stem cells may occur, . especially stem cells in cell cycle, hence in early stages of recovery of the population unduly low numerical values might be noted. In view of this observation, the concept of the colony-forming cell may have to be revised and instead the colony-forming property of the stem cell introduced. (author)

  19. Isolation of Human Innate Lymphoid Cells.

    Science.gov (United States)

    Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

    2018-06-29

    Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

  20. Colonic lymphoid follicles associated with colonic neoplasms

    International Nuclear Information System (INIS)

    Glick, S.N.; Teplick, S.K.; Ross, W.M.

    1986-01-01

    The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

  1. Progenitors of white dwarfs

    International Nuclear Information System (INIS)

    Drilling, J.S.; Schoenberner, D.

    1985-01-01

    Direct observational evidence is presented which indicates that the immediate progenitors of white dwarfs are the central stars of planetary nebulae (approximately 70%), other post-AGB objects (approximately 30%), and post-HB objects not massive enough to climb the AGB (approximately 0.3%). The combined birth rate for these objects is in satisfactory agreement with the death rate of main-sequence stars and the birth rate of white dwarfs

  2. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system

    Directory of Open Access Journals (Sweden)

    Enrique Montalvillo

    2014-05-01

    Full Text Available The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity. Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  3. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system.

    Science.gov (United States)

    Montalvillo, Enrique; Garrote, José Antonio; Bernardo, David; Arranz, Eduardo

    2014-05-01

    The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity.Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  4. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    OpenAIRE

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    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 ly...

  5. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

    In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I

  6. Total lymphoid irradiation of intractable rheumatoid arthritis

    International Nuclear Information System (INIS)

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

    1986-01-01

    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. (author)

  7. Innate lymphoid cells, precursors and plasticity.

    Science.gov (United States)

    Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

    2016-11-01

    Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. Radiotherapy of lymphoid diseases of the orbit

    International Nuclear Information System (INIS)

    Austin-Seymour, M.M.; Donaldson, S.S.; Egbert, P.R.; McDougall, I.R.; Kriss, J.P.

    1985-01-01

    Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. Two patients developed cataracts. Carefullly planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma

  9. 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.

  10. Homing of bone marrow lymphoid cells

    International Nuclear Information System (INIS)

    Yoshida, Y.; Osmond, D.G.

    1978-01-01

    DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Mapping of NKp46+ Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues

    Science.gov (United States)

    Tomasello, Elena; Yessaad, Nadia; Gregoire, Emilie; Hudspeth, Kelly; Luci, Carmelo; Mavilio, Domenico; Hardwigsen, Jean; Vivier, Eric

    2012-01-01

    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 γt (RORγt) 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 RORγt+ 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. PMID:23181063

  15. Masses of supernova progenitors

    International Nuclear Information System (INIS)

    Tinsley, B.M.

    1977-01-01

    The possible nature and masses of supernovae progenitors, and the bearing of empirical results on some unsolved theoretical problems concerning the origin of supernovae, are discussed. The author concentrates on two main questions: what is the lower mass limit for stars to die explosively and what stars initiate type I supernovae. The evidence considered includes local supernova rates, empirical estimates of msub(w) (the upper mass limit for death as a white dwarf), the distributions of supernovae among stellar populations in galaxies and the colors of supernova producing galaxies. (B.D.)

  16. Stroma cell priming in enteric lymphoid organ morphogenesis

    Directory of Open Access Journals (Sweden)

    Manuela eFerreira

    2012-07-01

    Full Text Available The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional Lymphoid Tissue inducer (LTi cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to secondary lymphoid organ formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood.

  17. [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

    Science.gov (United States)

    Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

    2015-03-09

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  18. Tertiary lymphoid structures in cancer and beyond.

    Science.gov (United States)

    Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

    2014-11-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. 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.

  20. Tertiary lymphoid organs in Takayasu Arteritis

    OpenAIRE

    Marc eClement; Marc eClement; Adrien eGaly; Patrick eBruneval; Marion eMorvan; Fabien eHyafil; Fabien eHyafil; Khadija eBenali; Nicoletta ePasi; Lydia eDeschamps; Quentin ePellenc; Quentin ePellenc; Thomas ePapo; Antonino eNicoletti; Antonino eNicoletti

    2016-01-01

    Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from t...

  1. Tertiary Lymphoid Organs in Takayasu Arteritis

    OpenAIRE

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    Objective The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Methods Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune ce...

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

    DEFF Research Database (Denmark)

    Dybkaer, Karen; Zhou, Guimei; Iqbal, Javeed

    2004-01-01

    acceptable gene coverage to serve as a comprehensive standard for gene expression profiling of lymphoid tissues. Our lymphoid standard was prepared from thymus, spleen, tonsil, and cell lines representing immature B cells, plasma cells, and natural killer (NK) cells, thus covering the entire spectrum...... of lymphoid cells and most stromal elements present in specialized lymphoid tissues. The two standards were co-hybridized on oligonucleotide microarrays containing 17,260 genes, and both had fluorescence intensities above background for approximately 85% of the genes. Despite the limited representation...... of lymphoid cells in the Stratagene standard, only 4.2% genes exhibited expression differences greater than 2-fold including only 0.35% with differences greater than 4-fold. Although the lymphoid standard reflected a more comprehensive representation of immune system-associated genes, the Stratagene standard...

  3. Stromal cell regulation of homeostatic and inflammatory lymphoid organogenesis

    Science.gov (United States)

    Kain, Matthew J W; Owens, Benjamin M J

    2013-01-01

    Summary Secondary lymphoid organs function to increase the efficiency of interactions between rare, antigen-specific lymphocytes and antigen presenting cells, concentrating antigen and lymphocytes in a supportive environment that facilitates the initiation of an adaptive immune response. Homeostatic lymphoid tissue organogenesis proceeds via exquisitely controlled spatiotemporal interactions between haematopoietic lymphoid tissue inducer populations and multiple subsets of non-haematopoietic stromal cells. However, it is becoming clear that in a range of inflammatory contexts, ectopic or tertiary lymphoid tissues can develop inappropriately under pathological stress. Here we summarize the role of stromal cells in the development of homeostatic lymphoid tissue, and assess emerging evidence that suggests a critical role for stromal involvement in the tertiary lymphoid tissue development associated with chronic infections and inflammation. PMID:23621403

  4. 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

    2016-01-01

    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. PMID:26951333

  5. Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells.

    Science.gov (United States)

    Scoville, Steven D; Freud, Aharon G; Caligiuri, Michael A

    2017-01-01

    Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development.

  6. Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo

    Directory of Open Access Journals (Sweden)

    Johanna Salvermoser

    2018-04-01

    Full Text Available Conventional dendritic cells (cDCs are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired.

  7. The Development of Adult Innate Lymphoid Cells

    Science.gov (United States)

    Yang, Qi; Bhandoola, Avinash

    2016-01-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  8. Total lymphoid irradiation in rhesus monkeys

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Maat, B.; Hogeweg, B.

    Total lymphoid irradiation (TLI) consists of three contiguous fields, a mantle, an inverted Y and a spleen field. TLI induces a state of immunosuppression in patients with Hodgkin disease or in small rodents. Infusion of allogeneic bone marrow cells into mice after TLI led to the development split haemopoietic chimerism and indefinite survival of skin grafts from the bone marrow donor. A protocol for TLI was developed for rhesus monkeys to attempt to verify these interesting observations in a pre-clinical animal model. (Auth.)

  9. Mesenchymal progenitor cells for the osteogenic lineage.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  10. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Directory of Open Access Journals (Sweden)

    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.

  12. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    International Nuclear Information System (INIS)

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    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

  13. Prion pathogenesis and secondary lymphoid organs (SLO)

    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 PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), 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. PMID:22895090

  14. [Comparative study of lymphoid follicles in mucosa of pharynx and mucosal associated lymphoid tissues in paranasal sinuses].

    Science.gov (United States)

    Zhai, Weigang; Yao, Min; Chen, Jue

    2013-08-01

    To study the relationship between the lymphoid follicles in mucous membrane of pharynx and mucosal associated lymphoid tissues (MALT). Ten folliculi obtained from 10 patients of follicular pharyngitis and mucosa taken form 10 patients of paranasal sinusitis were fixed in neutral formalin and embedded in paraffin. Sections were prepared, stained by H. E and by immunohistochemical method staining with S-100,and observe by light microscopy. We observed the morphology of lymphoid follicles in mucous membrane of pharynx with MALT in mucosa of paranasal sinusitis as the contrast. Lymphoid follicles in mucosa of pharynx compared with MALT in the mucosa of paranasal sinuses, there was no mantle zone, no typical germinal center and no mucosal epithelium, immunological staining with S-100 was week. The lymphoid follicles in mucosa of pharynx does not belong to the MALT.

  15. Radiation effects on cultured human lymphoid cells

    International Nuclear Information System (INIS)

    Johansson, L.; Nilsson, K.; Carlsson, J.; Larsson, B.; Jakobsson, P.

    1981-01-01

    The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed non-neoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. (Auth.)

  16. 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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Clinical epidemiological aspects of chronic lymphoid leukaemia

    International Nuclear Information System (INIS)

    Rodriguez Brunet, Marisol; Hernandez Galano, Geldris P; Suarez Beyries, Lidia C; Duverger Magdaleon, Ernesto

    2011-01-01

    A descriptive and retrospective study of 71 patients with chronic lymphoid leukemia, attended at the Hematology Service from 'Dr Juan Bruno Zayas Alfonso' Teaching General Hospital in Santiago de Cuba was carried out from January, 2001 to November, 2006, in order to identify some clinical epidemiological variables on them, to show the therapeutical variables more used, as well as to assess survival, mortality, and the main causes of the clinical entity. Elderly, male sex, and high risk category related to advanced stage were predominant in the series. The therapeutical schedule of chlorambucil and prednisone was the most used, achieving good results in the majority of the case material. The survival of patients, in general, ranged among 1-5 years, whereas deaths occurred due to disease progression, infectious respiratory processes, pro-lymphocytic transformation, second neoplasias, and strokes. (author)

  18. Tertiary lymphoid organs in Takayasu Arteritis

    Directory of Open Access Journals (Sweden)

    Marc eClement

    2016-04-01

    Full Text Available Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20, follicular dendritic cells (FDCs, CD21, and high endothelial venules (HEVs, PNAd was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment and follow up data were extracted from medical records.Results: Aorta specimens from Bentall procedures were available from 7 patients (five female, aged 22 to 57 years with TA. Surgical treatment was performed at TA diagnosis (n=4 or at a median of 108 months [84-156] after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient.. Of note, ectopic follicles containing CD21+ FDCs were found in all patients (4/4 with increased aortic FDG uptake before surgery but were absent in all but one patients (2/3 with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center–like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells.Conclusion: Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  19. Tertiary Lymphoid Organs in Takayasu Arteritis.

    Science.gov (United States)

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment, and follow-up data were extracted from medical records. Aorta specimens from Bentall procedures were available from seven patients (5 females, aged 22-57 years) with TA. Surgical treatment was performed at TA diagnosis (n = 4) or at a median of 108 months (84-156) after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient. Of note, ectopic follicles containing CD21(+) FDCs were found in all patients (4/4) with increased aortic (18)F-fluoro-deoxyglucose (FDG) uptake before surgery but were absent in all but one patients (2/3) with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center-like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells. Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  20. High-resolution CT of lymphoid interstitial pneumonia

    International Nuclear Information System (INIS)

    Vilgrain, V.; Frija, J.; Yana, C.; Couderc, L.J.; David, M.; Clauvel, J.P.; Laval-Jeantet, M.

    1989-01-01

    Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, 'ground-glass' opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient presents with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia [fr

  1. 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. © FASEB.

  2. 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. Copyright © 2016 by The American Association of Immunologists, Inc.

  3. 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.

    2015-01-01

    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.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  4. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

    Science.gov (United States)

    Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

    2017-02-14

    Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Bioengineering of Artificial Antigen Presenting Cells and Lymphoid Organs.

    Science.gov (United States)

    Wang, Chao; Sun, Wujin; Ye, Yanqi; Bomba, Hunter N; Gu, Zhen

    2017-01-01

    The immune system protects the body against a wide range of infectious diseases and cancer by leveraging the efficiency of immune cells and lymphoid organs. Over the past decade, immune cell/organ therapies based on the manipulation, infusion, and implantation of autologous or allogeneic immune cells/organs into patients have been widely tested and have made great progress in clinical applications. Despite these advances, therapy with natural immune cells or lymphoid organs is relatively expensive and time-consuming. Alternatively, biomimetic materials and strategies have been applied to develop artificial immune cells and lymphoid organs, which have attracted considerable attentions. In this review, we survey the latest studies on engineering biomimetic materials for immunotherapy, focusing on the perspectives of bioengineering artificial antigen presenting cells and lymphoid organs. The opportunities and challenges of this field are also discussed.

  6. Morphology of mucosa-associated lymphoid tissue in odontocetes.

    Science.gov (United States)

    Silva, Fernanda M O; Guimarães, Juliana P; Vergara-Parente, Jociery E; Carvalho, Vitor L; Carolina, Ana; Meirelles, O; Marmontel, Miriam; Oliveira, Bruno S S P; Santos, Silvanise M; Becegato, Estella Z; Evangelista, Janaina S A M; Miglino, Maria Angelica

    2016-09-01

    This study describes the mucosa-associated lymphoid tissue (MALT) in odontocetes from the Brazilian coast and freshwater systems. Seven species were evaluated and tissue samples were analyzed by light, scanning and transmission electron microscopy, and immunohistochemistry. Laryngeal tonsil was a palpable oval mass located in the larynx, composed of a lymphoepithelial complex. Dense collections of lymphocytes were found in the skin of male fetus and calf. Clusters of lymphoid tissue were found in the uterine cervix of a reproductively active juvenile female and along the pulmonary artery of an adult female. Lymphoid tissues associated with the gastrointestinal tract were characterized by diffusely arranged or organized lymphocytes. The anal tonsil was composed of an aggregate of lymphoid tissue occurring exclusively in the anal canal, being composed of squamous epithelium branches. MALT was present in different tissues and organic systems of cetaceans, providing constant protection against mucosal pathogens present in their environment. © 2016 Wiley Periodicals, Inc.

  7. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    International Nuclear Information System (INIS)

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B.

    1991-01-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy

  8. Early lymphoid lesions: conceptual, diagnostic and clinical challenges

    OpenAIRE

    Ganapathi, Karthik A.; Pittaluga, Stefania; Odejide, Oreofe O.; Freedman, Arnold S.; Jaffe, Elaine S.

    2014-01-01

    There are no “benign lymphomas”, a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. Recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. Some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as BCL2/IGH and CCND1/IGH transl...

  9. 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.

  10. Lymphoid Aggregates That Resemble Tertiary Lymphoid Organs Define a Specific Pathological Subset in Metal-on-Metal Hip Replacements

    Science.gov (United States)

    Barone, Francesca; Hardie, Debbie L.; Matharu, Gulraj S.; Davenport, Alison J.; Martin, Richard A.; Grant, Melissa; Mosselmans, Frederick; Pynsent, Paul; Sumathi, Vaiyapuri P.; Addison, Owen; Revell, Peter A.; Buckley, Christopher D.

    2013-01-01

    Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants. PMID:23723985

  11. The poster as modernist progenitor

    Directory of Open Access Journals (Sweden)

    Katherine Hauser

    2015-12-01

    Full Text Available Ruth E. Iskin’s The Poster: Art, Advertising. Design, and Collecting, 1860s-1900s positions the late-nineteenth-century advertising poster as the progenitor of valued modernist practices typically attached solely to photography and film. Modernist biases separating high art from mass culture account for scholars ignoring posters, however the poster ushered in an innovative reductive graphic style as well as pioneered the notion of multiple originals.

  12. PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS

    Energy Technology Data Exchange (ETDEWEB)

    Moriya, Takashi J., E-mail: takashi.moriya@ipmu.jp [Kavli Institute for the Physics and Mathematics of the Universe, Todai Institutes for Advanced Study, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8583 (Japan)

    2012-05-01

    Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with ionization temperature higher than the electron temperature, has been recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.

  13. Immunosuppressive effect of total lymphoid irradiation

    International Nuclear Information System (INIS)

    Bendel, V.; Medizinische Hochschule Hannover

    1981-01-01

    Contrary to the immunosuppression by means of wholebody irradiation which is known for a long while but connected with considerable side effects and risks, the total lymphoid irradiation (TLI) is a new possibility of immunosuppression the tolerance of which by man is known by virtue of long-standing experiences with the treatment of malignant lymphatic system diseases. In connexion with organ transplantations, TLI might possibly soon be important for the radiotherapeutist. In the experimentation on animals, the unspecific immunosuppression induced by TLI causes a prolonged survival time of allogeneic skin and organ grafts in certain mammals. Furthermore, a formation of blood chimeras combined with specific, permanent tolerance of organ grafts from the bone marrow donor can be caused by bone marrow transplantation after TLI. First experiences with man have been made. In the German literature, TLI has not been mentioned yet. In the present study, a summary is given on the Anglo-Saxon literature, and the first own experiments with regard to the problem of irradiation dose and transplantation interval are presented. (orig.) [de

  14. Epigenomic Views of Innate Lymphoid Cells.

    Science.gov (United States)

    Sciumè, Giuseppe; Shih, Han-Yu; Mikami, Yohei; O'Shea, John J

    2017-01-01

    The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.

  15. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue.

    Science.gov (United States)

    Martinet, Kim Zita; Bloquet, Stéphane; Bourgeois, Christine

    2014-01-01

    CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary

  16. Total lymphoid irradiation for multiple sclerosis

    International Nuclear Information System (INIS)

    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

  17. 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. PMID:27774092

  18. Characterization of nasal cavity-associated lymphoid tissue in ducks.

    Science.gov (United States)

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2014-05-01

    The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. Copyright © 2014 Wiley Periodicals, Inc.

  19. Innate lymphoid cells: models of plasticity for immune homeostasis and rapid responsiveness in protection.

    Science.gov (United States)

    Almeida, F F; Belz, G T

    2016-09-01

    Innate lymphoid cells (ILCs) have stormed onto the immune landscape as "newly discovered" cell types. These tissue-resident sentinels are enriched at mucosal surfaces and engage in complex cross talk with elements of the adaptive immune system and microenvironment to orchestrate immune homeostasis. Many parallels exist between innate cells and T cells leading to the initial partitioning of ILCs into rather rigid subsets that reflect their "adaptive-like" effector cytokines profiles. ILCs themselves, however, have unique attributes that are only just beginning to be elucidated. These features result in complementarity with, rather than complete duplication of, functions of the adaptive immune system. Key transcription factors determine the pathway of differentiation of progenitors towards an ILC1, ILC2, or ILC3 subset. Once formed, flexibility in the responses of these subsets to stimuli unexpectedly allows transdifferentation between the different subsets and the acquisition of altered phenotypes and function. This provides a mechanism for rapid innate immune responsiveness. Here, we discuss the models of differentiation for maintenance and activation of tissue-resident ILCs in maintaining immune homeostasis and protection.

  20. [Rectal tonsil or lymphoid follicular hyperplasia of the rectum].

    Science.gov (United States)

    Trillo Fandiño, L; Arias González, M; Iglesias Castañón, A; Fernández Eire, M P

    2014-01-01

    The rectal tonsil is a reactive proliferation of lymphoid tissue located in the rectum. The morphology of the lymphoid proliferation of the colon is usually polypoid or, less commonly, nodular. Only in exceptional cases does lymphoid proliferation of the colon present as a mass in the rectum (rectal tonsil), although this is the most common presentation in middle-aged patients. It is important to be familiar with the rectal tonsil because in cases of exuberant growth it can be difficult to distinguish it from other types of masses. We present the case of rectal tonsil in a four-year-old girl. We describe the magnetic resonance imaging findings and review the literature. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  1. Induction and Analysis of Bronchus-Associated Lymphoid Tissue.

    Science.gov (United States)

    Fleige, Henrike; Förster, Reinhold

    2017-01-01

    Bronchus-associated lymphoid tissue (BALT) forms spontaneously in the lung after pulmonary infection and has been identified as a highly organized lymphoid structure supporting the efficient priming of T cells in the lung. To explore the mechanisms and instructive signals controlling BALT neogenesis we used both, a single dose of vaccinia virus MVA and repeated inhalations of heat-inactivated Pseudomonas aeruginosa (P. aeruginosa). Intranasal administration of both pathogens induces highly organized BALT but distinct pathways and molecules are used to promote the development of BALT. Here, we describe the induction and phenotype of the distinct types of BALT as well as the immunofluorescence microscopy-based analysis of the induced lymphoid tissue in the lung.

  2. B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis

    NARCIS (Netherlands)

    Cantaert, Tineke; Kolln, Johanna; Timmer, Trieneke; van der Pouw Kraan, Tineke C.; Vandooren, Bernard; Thurlings, Rogier M.; Cañete, Juan D.; Catrina, Anca I.; Out, Theo; Verweij, Cor L.; Zhang, Yiping; Tak, Paul P.; Baeten, Dominique

    2008-01-01

    B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may

  3. IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage.

    Science.gov (United States)

    Barik, Subhasis; Miller, Mindy M; Cattin-Roy, Alexis N; Ukah, Tobechukwu K; Chen, Weirong; Zaghouani, Habib

    2017-10-15

    Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Rα and IL-13Rα1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR + ETPs, but not HR - ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPα, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR + ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR - ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development. Copyright © 2017 by The American Association of Immunologists, Inc.

  4. Progenitor's Signatures in Type Ia Supernova Remnants

    NARCIS (Netherlands)

    Chiotellis, A.; Kosenko, D.; Schure, K.M.; Vink, J.

    2013-01-01

    The remnants of Type Ia supernovae (SNe Ia) can provide important clues about their progenitor histories. We discuss two well-observed supernova remnants (SNRs) that are believed to have resulted from SNe Ia, and use various tools to shed light on the possible progenitor histories. We find that

  5. Pulpal progenitors and dentin repair.

    Science.gov (United States)

    Harichane, Y; Hirata, A; Dimitrova-Nakov, S; Granja, I; Goldberg, A; Kellermann, O; Poliard, A

    2011-07-01

    Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-based therapies.

  6. Innate Lymphoid Cells in Intestinal Inflammation

    Science.gov (United States)

    Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of

  7. Innate Lymphoid Cells in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Alessandra Geremia

    2017-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an

  8. Apparent clusters of childhood lymphoid malignancy in Northern England

    International Nuclear Information System (INIS)

    Craft, A.W.; Openshaw, S.; Birch, J.

    1984-01-01

    The authors have reanalysed their previous data on the incidence of childhood malignancy in the North of England by very small geographical areas. Seascale, which ranks first by Poisson probability for all lymphoid malignancies is the village closest to the Sellafield plant. However, it is not unique in the region; nor are wards of apparent excess confined to coastal areas of Cumbria. The highest rate of lymphoid malignancies is in Whittingham, a village in north Northumberland. For other varieties of childhood cancer, there is a similar spread of 'Highly ranked', but different, wards throughout the region. (U.K.)

  9. 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. PMID:24418741

  10. Mature lymphoid malignancies: origin, stem cells, and chronicity

    DEFF Research Database (Denmark)

    Husby, Simon; Grønbæk, Kirsten

    2017-01-01

    after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell...... population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source...

  11. Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

    International Nuclear Information System (INIS)

    Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

    1981-01-01

    High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here

  12. Transplanting oligodendrocyte progenitors into the adult CNS

    International Nuclear Information System (INIS)

    Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.

    1997-01-01

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

  13. Functional differences between human NKp44(-) and NKp44(+) RORC+ innate lymphoid cells

    NARCIS (Netherlands)

    Hoorweg, Kerim; Peters, Charlotte P.; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M.; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human 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 in human

  14. File list: InP.Bld.50.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: ALL.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Lymphoid_cells mm9 Input control Blood Lymphoid cells SRX971601,SR...X021894 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Lymphoid_cells.bed ...

  18. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review.

    Science.gov (United States)

    Casteleyn, C; Doom, M; Lambrechts, E; Van den Broeck, W; Simoens, P; Cornillie, P

    2010-06-01

    The lymphoid tissue that is associated with the intestinal tract, the so-called gut-associated lymphoid tissue (GALT), is well developed in the chicken. Depending on the location, it is present as aggregations of lymphoid cells, or organized in lymphoid follicles and tonsils. From proximal to distal, the intestinal tract contains a pharyngeal tonsil, diffuse lymphoid tissue and lymphoid follicles in the cervical and thoracic parts of the oesophagus, an oesophageal tonsil, diffuse lymphoid tissue in the proventriculus, a pyloric tonsil, Peyer's patches, Meckel's diverticulum, two caecal tonsils, diffuse lymphoid tissue in the rectum, the bursa of Fabricius, and diffuse lymphoid tissue in the wall of the proctodeum. The lymphoid tissues are frequently covered by a lympho-epithelium that is infiltrated by lymphoid cells. Such an epithelium often contains M or microfold cells, which are specialized in antigen sampling and transport antigens to the underlying lymphoid tissue. A solid knowledge of the avian GALT could contribute to the development of vaccines to be administered orally. Additionally, immune stimulation via pre- and probiotics is based on the presence of a well-developed intestinal immune system.

  19. File list: ALL.Bld.50.AllAg.Lymphoid_cells [Chip-atlas[Archive

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  20. File list: InP.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

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

    Lifescience Database Archive (English)

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  2. 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

  3. Innate lymphoid cells and parasites: Ancient foes with shared history.

    Science.gov (United States)

    Neill, D R; Fallon, P G

    2018-02-01

    This special issue of Parasite Immunology charts the rapid advances made in our understanding of the myriad interactions between innate lymphoid cells and parasites and how these interactions have shaped our evolutionary history. Here, we provide an overview of the issue and highlight key findings from studies in mice and man. © 2017 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

  4. Developmental acquisition of regulomes underlies innate lymphoid cell functionality

    Science.gov (United States)

    Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both usages of effector molecules and ·transcription factors. To better understand ILC subsets and their relationship with Th cells, we measur...

  5. Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.

    Science.gov (United States)

    Mortha, Arthur; Burrows, Kyle

    2018-01-01

    Innate lymphoid cells (ILCs) are an essential component of the innate immune system in vertebrates. They are developmentally rooted in the lymphoid lineage and can diverge into at least three transcriptionally distinct lineages. ILCs seed both lymphoid and non-lymphoid tissues and are locally self-maintained in tissue-resident pools. Tissue-resident ILCs execute important effector functions making them key regulator in tissue homeostasis, repair, remodeling, microbial defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few sensory elements for the recognition of non-self and thus depend on extrinsic cellular sensory elements residing within the tissue. Myeloid cells, including mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to translate environmental cues into an effector profile that instructs lymphocyte responses. The adaptation of myeloid cells to the tissue state thus influences the effector program of ILCs and serves as an example of how environmental signals are integrated into the function of ILCs via a tissue-resident immune cell cross talks. This review summarizes our current knowledge on the role of myeloid cells in regulating ILC functions and discusses how feedback communication between ILCs and myeloid cells contribute to stabilize immune homeostasis in order to maintain the healthy state of an organ.

  6. ID’ing Innate and Innate-like Lymphoid Cells

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.

    2014-01-01

    Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285

  7. Innate lymphoid cells--a proposal for uniform nomenclature

    NARCIS (Netherlands)

    Spits, Hergen; Artis, David; Colonna, Marco; Diefenbach, Andreas; Di Santo, James P.; Eberl, Gerard; Koyasu, Shigeo; Locksley, Richard M.; McKenzie, Andrew N. J.; Mebius, Reina E.; Powrie, Fiona; Vivier, Eric

    2013-01-01

    Innate lymphoid cells (ILCs) are a family of developmentally related cells that are involved in immunity and in tissue development and remodelling. Recent research has identified several distinct members of this family. Confusingly, many different names have been used to characterize these newly

  8. ID'ing innate and innate-like lymphoid cells.

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C; Kee, Barbara L

    2014-09-01

    The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Innate lymphoid cells: the new kids on the block.

    Science.gov (United States)

    Withers, David R; Mackley, Emma C; Jones, Nick D

    2015-08-01

    The purpose of this article is to review recent advances in our understanding of innate lymphoid cell function and to speculate on how these cells may become activated and influence the immune response to allogeneic tissues and cells following transplantation. Innate lymphoid cells encompass several novel cell types whose wide-ranging roles in the immune system are only now being uncovered. Through cytokine production, cross-talk with both haematopoietic and nonhaematopoietic populations and antigen presentation to T cells, these cells have been shown to be key regulators in maintaining tissue integrity, as well as initiating and then sustaining immune responses. It is now clear that innate lymphoid cells markedly contribute to immune responses and tissue repair in a number of disease contexts. Although experimental and clinical data on the behaviour of these cells following transplantation are scant, it is highly likely that innate lymphoid cells will perform similar functions in the alloimmune response following transplantation and therefore may be potential therapeutic targets for manipulation to prevent allograft rejection.

  10. 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.

  11. 'Managing' the immune system with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.

    1981-01-01

    Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis

  12. Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases

    NARCIS (Netherlands)

    Shikhagaie, Medya M.; Germar, Kristine; Bal, Suzanne M.; Ros, Xavier Romero; Spits, Hergen

    2017-01-01

    Innate lymphoid cells (ILCs) are important in the regulation of barrier homeostasis. These cells do not express T cell receptors but share many functional similarities with T helper cells and cytotoxic CD8(+) T lymphocytes. ILCs are divided into three groups, namely group 1 ILCs, group 2 ILCs and

  13. 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

  14. Induction of secondary and tertiary lymphoid structures in the skin.

    NARCIS (Netherlands)

    Cupedo, T.; Jansen, W.; Kraal, G.; Mebius, R.E.

    2004-01-01

    During embryogenesis a developmental program leading to the formation of lymph nodes and Peyer's patches is initiated. We now show that lymph node-like structures as well as tertiary lymphoid structures can ectopically be induced by intradermal injection of newborn lymph node-derived cells.

  15. Progenitor cells in pulmonary vascular remodeling

    Science.gov (United States)

    Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.

    2011-01-01

    Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

  16. H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anne-France Petit-Bertron

    Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

  17. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    International Nuclear Information System (INIS)

    Park, Charn Il; Han, Man Chung

    1981-01-01

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 ± 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 ± 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers

  18. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Charn Il; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1981-06-15

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 {+-} 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 {+-} 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers.

  19. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

    Science.gov (United States)

    Melo-Gonzalez, Felipe; Hepworth, Matthew R

    2017-03-01

    Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

  20. Clinical outcomes of childhood x-irradiation for lymphoid hyperplasia

    International Nuclear Information System (INIS)

    Pottern, L.M.

    1987-01-01

    A prospective study was conducted to explore the relationship between childhood x-irradiation for lymphoid hyperplasia and the subsequent development of thyroid gland and other head and neck disorders. All individuals under 18 years of age who were x-irradiated for lymphoid hyperplasia during the years 1938-69 at Children's Hospital Medical Center, Boston comprised the exposed population. The comparison group consisted of non-exposed, surgically treated individuals. The study included a health questionnaire and a clinical examination component. A history of thyroid cancer was reported by 11 exposed subjects and no non-exposed subjects. Significantly elevated standardized incidence ratios of thyroid cancer were seen for both exposed males and females, 19.9 and 12.1, respectively. The average thyroid radiation dose was 25.8 rads and the mean latency period was 17.3 years

  1. Total lymphoid irradiation in refractory systemic lupus erythematosus

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  2. Beyond NK cells: the expanding universe of innate lymphoid cells.

    Science.gov (United States)

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  3. Beyond NK cells: the expanding universe of Innate Lymphoid Cells.

    Directory of Open Access Journals (Sweden)

    Marina eCella

    2014-06-01

    Full Text Available For a long time NK cells were thought to be the only immune innate lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different Innate Lymphoid Cells found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. ILC populations closely mirror the phenotype of adaptive Thelper subsets in their ability to secrete soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response appropriate to the incoming insult. Here we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  4. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    International Nuclear Information System (INIS)

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-01-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease

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

    International Nuclear Information System (INIS)

    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

  6. Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

    Science.gov (United States)

    Maglione, Paul J; Cols, Montserrat; Cunningham-Rundles, Charlotte

    2017-10-05

    Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

  7. 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

  8. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

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

    1985-01-01

    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

  9. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue

    OpenAIRE

    Martinet , Kim ,; Bloquet , Stéphane; Bourgeois , Christine

    2014-01-01

    International audience; BackgroundCD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue ...

  10. Heterogeneity of limbal basal epithelial progenitor cells.

    Science.gov (United States)

    Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

    2010-11-01

    Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

  11. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  12. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  13. Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

    Science.gov (United States)

    Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

    2013-11-01

    Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

  14. Skin-associated lymphoid tissues (SALT): origins and functions

    International Nuclear Information System (INIS)

    Streilein, J.W.

    1983-01-01

    The skin has an unusual set of immunologic requirements. It is confronted by a specialized set of pathogenic organisms and environmental chemicals that represent a distinctive spectrum of antigenic specificities. Skin is subjected to physicochemical stresses such as irradiation with ultraviolet light that alter dramatically its immunologic properties. It is proposed that nature has provided skin with a unique collection of lymphoid cells, reticular cells, and organized lymphoid organs to deal with these special demands. Evidence in favor of the existence of skin-associated lymphoid tissues (SALT) includes (1) the cutaneous microenvironment is capable on its own of accepting, processing, and presenting nominal antigen; (2) strategically located peripheral lymph nodes are able to accept immunogenic signals derived from skin; (3) subsets of T lymphocytes display differential affinity for skin and its associated peripheral nodes; and (4) acquisition of this affinity by T cells is determined at least in part by differentiation signals received in situ from resident cutaneous cells. Responsibility for the establishment and integration of SALT rests with keratinocytes, Langerhans cells, and immunocompetent lymphocytes, each of which contributes uniquely to the synthesis. Together they provide skin with immune surveillance that effectively prejudices against the development of cutaneous neoplasms and persistent infection with intracellular pathogens. In patients who have been under long-term immunosuppressive therapy, the large majority of nonlymphoid malignancies arise within the skin, rather than other types of tissues. These data suggest that immune surveillance, once thought to be an immune defense operative in all somatic tissues, is a specialized immune function dedicated to the skin and mediated by SALT

  15. Development of venetoclax for therapy of lymphoid malignancies

    Directory of Open Access Journals (Sweden)

    Zhu H

    2017-03-01

    Full Text Available Huayuan Zhu,1,2 Alexandru Almasan1 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; 2Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China Abstract: B-cell lymphoma-2 (BCL-2 family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199 is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients. Also, unlike the other targeted agents, it is effective against tumor cells that reside in the blood marrow. Despite its promising outcome in CLL, preclinical data have already uncovered mechanistic insights underlying venetoclax resistance, such as upregulation of MCL-1 or BCL-xL expression and protective signaling from the microenvironment. In this review, we describe the role of the BCL-2 family in the pathogenesis of B-cell lymphoid malignancies, the development of venetoclax, and its current clinical outcome in CLL and other B-cell malignancies. We also discuss the resistance mechanisms that develop following venetoclax therapy, potential strategies to overcome them, and how this knowledge can be translated into clinical applications. Keywords: BCL-2, BCL-xL, chronic lymphocytic leukemia, MCL-1, venetoclax

  16. 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

  17. Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34+ bone marrow cells, following gamma irradiation in cynomolgus macaques

    Directory of Open Access Journals (Sweden)

    Auregan Gwenaelle

    2008-06-01

    Full Text Available Abstract Background Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myeloablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques. Results The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% ± 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudotyped and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% ± 10%. A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producingeGFP were detected as early as three days after transplantation, and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion The transplantation of CD34+ bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T- and B-lymphocyte, thrombocyte and red blood cell compartments.

  18. DNMT3AR882H mutant and Tet2 inactivation cooperate in the deregulation of DNA methylation control to induce lymphoid malignancies in mice

    DEFF Research Database (Denmark)

    Scourzic, L; Couronné, L; Pedersen, Marianne Terndrup

    2016-01-01

    malignancies with one mouse developing an AITL-like disease, two mice presenting acute myeloid leukemia (AML)-like and two others T-cell acute lymphoblastic leukemia (T-ALL)-like diseases within 6 months following transplantation. Serial transplantations of DNMT3A(R882H) Tet2(-/-) progenitors led...... to a differentiation bias toward the T-cell compartment, eventually leading to AITL-like disease in 9/12 serially transplanted recipients. Expression profiling suggested that DNMT3A(R882H) Tet2(-/-) T-ALLs resemble those of NOTCH1 mutant. Methylation analysis of DNMT3A(R882H) Tet2(-/-) T-ALLs showed a global increase...... in DNA methylation affecting tumor suppressor genes and local hypomethylation affecting genes involved in the Notch pathway. Our data confirm the transformation potential of DNMT3A(R882H) Tet2(-/-) progenitors and represent the first cooperative model in mice involving Tet2 inactivation driving lymphoid...

  19. Isolation and characterization of mouse innate lymphoid cells.

    Science.gov (United States)

    Halim, Timotheus Y F; Takei, Fumio

    2014-08-01

    Innate lymphoid cells (ILCs) are rare populations of cytokine-producing lymphocytes and are divided into three groups, namely ILC1, ILC2, and ILC3, based on the cytokines that they produce. They comprise less than 1% of lymphocytes in mucosal tissues and express no unique cell surface markers. Therefore, they can only be identified by combinations of multiple cell surface markers and further characterized by cytokine production in vitro. Thus, multicolor flow cytometry is the only reliable method to purify and characterize ILCs. Here we describe the methods for cell preparation, flow cytometric analysis, and purification of murine ILC2 and ILC3. Copyright © 2014 John Wiley & Sons, Inc.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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. (author)

  1. Cataclysmic Variables as Supernova Ia Progenitors

    Directory of Open Access Journals (Sweden)

    Stella Kafka

    2012-06-01

    Full Text Available Although the identification of the progenitors of type Ia supernovae (SNeIa remains controversial, it is generally accepted that they originate from binary star systems in which at least one component is a carbon-oxygen white dwarf (WD; those systems are grouped under the wide umbrella of cataclysmic variables. Current theories for SNeIa progenitors hold that, either via Roche lobe overflow of the companion or via a wind, the WD accumulates hydrogen or helium rich material which is then burned to C and O onto the WD’s surface. However, the specifics of this scenario are far from being understood or defined, allowing for a wealth of theories fighting for attention and a dearth of observations to support them. I discuss the latest attempts to identify and study those controversial SNeIa progenitors. I also introduce the most promising progenitor in hand and I present observational diagnostics that can reveal more members of the category.

  2. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo; Pagliari, Francesca

    2017-01-01

    by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient

  3. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R. [Department of Astronomy, University of Washington Seattle, Box 351580, WA 98195 (United States); Murphy, Jeremiah W. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Dolphin, Andrew E., E-mail: zachjenn@uw.edu, E-mail: adolphin@raytheon.com [Raytheon, 1151 East Hermans Road, Tucson, AZ 85706 (United States)

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  4. 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

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

    Science.gov (United States)

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

    2014-11-01

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

  6. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling

    NARCIS (Netherlands)

    Spits, Hergen; Di Santo, James P.

    2011-01-01

    Research has identified what can be considered a family of innate lymphoid cells (ILCs) that includes not only natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells but also cells that produce interleukin 5 (IL-5), IL-13, IL-17 and/or IL-22. These ILC subsets are developmentally related,

  7. Innate Lymphoid Cells: Emerging Insights in Development, Lineage Relationships, and Function

    NARCIS (Netherlands)

    Spits, Hergen; Cupedo, Tom

    2012-01-01

    Innate lymphoid cells (ILCs) are immune cells that lack a specific antigen receptor yet can produce an array of effector cytokines that in variety match that of T helper cell subsets. ILCs function in lymphoid organogenesis, tissue remodeling, antimicrobial immunity, and inflammation, particularly

  8. Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

    Directory of Open Access Journals (Sweden)

    Suzanne R. Kalb

    2017-06-01

    Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

  9. Innate Lymphoid Cells in HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  11. [The lymph nodes imprint for the diagnosis of lymphoid neoplasms].

    Science.gov (United States)

    Peniche-Alvarado, Carolina; Ramos-Peñafiel, Christian Omar; Martínez-Murillo, Carlos; Romero-Guadarrama, Mónica; Olarte-Carrillo, Irma; Rozen-Fuller, Etta; Martínez-Tovar, Adolfo; Collazo-Jaloma, Juan; Mendoza-García, Carlos Alberto

    2013-01-01

    lymphoma is the most frequent lymphoid neoplasm in our country. Its diagnosis is based on histopathological findings. The lymph node imprint has been used for more than 40 years. The aim was to establish the sensitivity, specificity, positive predictive value and negative predictive value of lymph node imprint and estimate the inter-observer rate. we did an observational, retrospective, prolective study, based on the lymph node imprint obtained by excisional biopsies over a period of 6 years. the inclusion criteria was met on 199 samples, 27.1 % were considered as reactive (n = 54), 16.1 % Hodgkin lymphoma (n = 32), 40.2 % (n = 80) non-Hodgkin lymphoma and 16.6 % (n = 33) as metastatic carcinoma. Comparing with the final histopathology report, the sensitivity and specificity of lymph node imprint were 88 % (0.81-0.95) and 64 % (0.55-0.73) respectively, the positive predictive value was 67 % (0.59-0.76) and the negative predictive value was 86 % (0.79-0.94). The interobserver kappa index was 0.467. the lymph node imprint remains as a useful tool for the diagnosis of lymphoid neoplasm. The agreement between observers was acceptable.

  12. Human innate lymphoid cells (ILCs) in filarial infections.

    Science.gov (United States)

    Bonne-Année, S; Nutman, T B

    2018-02-01

    Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  13. Innate lymphoid cells in normal and disease: An introductory overview.

    Science.gov (United States)

    Moretta, Lorenzo; Locatelli, Franco

    2016-11-01

    Innate lymphoid cells (ILC) represent a novel group of lymphocytes that, different from T and B-lymphocytes lack recombinant activating genes (RAG-1 or RAG-2) and thus do not express rearranged antigen-specific receptors. Members of this family, i.e. NK cells, have been known since long time, while the other ILCs have been discovered only in recent years, possibly because of their predominant localization in tissues, primarily in mucosal tissues, skin and mucosa-associated lymphoid organs. ILC have been grouped in three major subsets on the basis of their phenotypic and functional features as well as of their dependency on given transcription factors (TF). Briefly, ILC-1 are dependent on T-bet TF and produce interferon (IFN)-γ. Group 2 ILC (ILC2) express GATA-3 TF and produce IL-5, IL-4 and IL-13 (Type 2) cytokines while group 3 ILC (ILC3) express RORγt TF and produce IL-17 and IL-22. ILC provide early defenses against pathogens and intervene in the repair of damaged tissues. ILC activation is mediated by cytokines (specifically acting on different ILC groups) and/or by activating receptors that are, at least in part, the same that had been previously identified in NK cells [1]. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  14. The Yin and Yang of Innate Lymphoid Cells in Cancer.

    Science.gov (United States)

    Carrega, Paolo; Campana, Stefania; Bonaccorsi, Irene; Ferlazzo, Guido

    2016-11-01

    The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  15. Emerging concepts and future challenges in innate lymphoid cell biology

    Science.gov (United States)

    Artis, David

    2016-01-01

    Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role. PMID:27811053

  16. Innate Lymphoid Cells in HIV/SIV Infections.

    Science.gov (United States)

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  17. Trafficking of α-L-fucosidase in lymphoid cells

    International Nuclear Information System (INIS)

    DiCioccio, R.A.; Brown, K.S.

    1987-01-01

    The quantity of α-L-fucosidase in human serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. To investigate this, lymphoid cell lines derived from individuals with either low, intermediate or high α-L-fucosidase in serum were established. Steady state levels of extracellular α-L-fucosidase protein and activity overlapped among the cell lines. Thus, in vivo serum phenotypes of α-L-fucosidase are not adequately expressed in this system. α-L-Fucosidase was also metabolically labelled with 35 S-methionine, immunoprecipitated, and examined by SDS-PAGE. Cells pulse-labelled from 0.25-2 h had a major intracellular form of enzyme (Mr = 58,000). Cells pulsed for 1.5 h and chased for 21 h with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. Cells treated with chloroquine had only the 58,000-form both intra- and extra-cellularly. Moreover, chloroquine did not effect the quantitative distribution of α-L-fucosidase between cells and medium. In fibroblasts, chloroquine enhanced the secretion of newly made lysosomal enzymes and blocked the processing of intercellular enzyme forms from a higher to a lower molecular mass. Thus, there are trafficking differences between α-L-fucosidase in lymphoid cells and lysosomal enzymes in fibroblasts. This suggests that alternative targeting mechanisms for lysosomal enzymes exist in these cells

  18. Gut-associated Lymphoid Tissue (GALT) Carcinoma or Dome Carcinoma?

    Science.gov (United States)

    Rubio, Carlos A; Schmidt, Peter T

    2016-10-01

    The vast majority of colorectal carcinomas (CRCs) evolve from mucosa not associated to lymphoid tissues aggregates via the adenoma-carcinoma sequence or via the serrated pathway. Rarely CRCs evolve from gut mucosa associated to lymphoid tissue (GALT). Based on the presence of a circumscribed elevation in the colorectal mucosa, GALT carcinomas are also referred to as dome carcinomas (DC). Descriptions of the surface mucosa covering 21 GALT-CRCs appearing in pathological reports were reviewed. Three of the 21 GALT-CRCs fulfilled the criteria of dome carcinoma. Of the remaining 18 GALT-CRCs, nine were described as polypoid lesions, five as plaque-like lesions, two as sessile elevated lesions or mass, one as ulcerated and one as histological finding. Hence, only 14.3% (n=3) of the 21 GALT-CRCs displayed a dome configuration, whereas the majority, 85.7% (n=18), exhibited structures other than dome shapes at gross or at histologic examination. It becomes apparent that by using "dome" in addressing carcinomas in the colorectal mucosa, many cases of GALT carcinomas might be overlooked. Another drawback of using the "dome" nomenclature is that dome-like outlines may be detected in small metastatic tumors in the submucosa or in small colorectal carcinomas not arising from GALT mucosa. Instead, by using "GALT carcinoma", that is the histologic diagnosis in addressing these neoplasias, all cases of GALT-CRCs will be included. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

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

    1981-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy

  20. Postirradiation recovery of lymphoid cells in the rat

    International Nuclear Information System (INIS)

    Farnsworth, A.; Wotherspoon, J.S.; Dorsch, S.E.

    1988-01-01

    Whole-body irradiation has been extensively used to remove immune responsiveness in rodent recipients in adoptive allograft assays. This study was undertaken to determine the relative radioresistance and the tempo of regeneration, following whole-body irradiation, of cells involved in the allograft response. Six distinct cell populations have been identified in the lymphoid tissues of rats subjected to sublethal whole-body irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated controls. NK cells, macrophages, and plasma cells, which are present in very low numbers in cell suspensions prepared from normal lymphoid tissues, made up a significant proportion of the residual/regenerating population in the tissues of rats recovering from whole-body irradiation. More significantly perhaps, the mature T cell populations showed a significant increase in the T cytotoxic/suppressor to T helper cell ratio. These observations support the suggestion that a number of the cell types within the mixed cell population observed in the rejecting indicator grafts of irradiated recipients in adoptive allograft assays are host derived. The finding that the T cytotoxic/suppressor population is apparently more radioresistant than the T helper population supports a conclusion that graft rejection in irradiated recipients, restored with pure populations of T helper cells, may not be directly mediated by the injected cells but may be the result of collaboration between these and host-derived cytotoxic cell populations

  1. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-01-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  2. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    Science.gov (United States)

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  3. Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

    Science.gov (United States)

    Gori, Jennifer L.; Butler, Jason M.; Chan, Yan-Yi; Chandrasekaran, Devikha; Poulos, Michael G.; Ginsberg, Michael; Nolan, Daniel J.; Elemento, Olivier; Wood, Brent L.; Adair, Jennifer E.; Rafii, Shahin; Kiem, Hans-Peter

    2015-01-01

    Pluripotent stem cells (PSCs) represent an alternative hematopoietic stem cell (HSC) source for treating hematopoietic disease. The limited engraftment of human PSC–derived (hPSC-derived) multipotent progenitor cells (MPP) has hampered the clinical application of these cells and suggests that MPP require additional cues for definitive hematopoiesis. We hypothesized that the presence of a vascular niche that produces Notch ligands jagged-1 (JAG1) and delta-like ligand-4 (DLL4) drives definitive hematopoiesis. We differentiated hes2 human embryonic stem cells (hESC) and Macaca nemestrina–induced PSC (iPSC) line-7 with cytokines in the presence or absence of endothelial cells (ECs) that express JAG1 and DLL4. Cells cocultured with ECs generated substantially more CD34+CD45+ hematopoietic progenitors compared with cells cocultured without ECs or with ECs lacking JAG1 or DLL4. EC-induced cells exhibited Notch activation and expressed HSC-specific Notch targets RUNX1 and GATA2. EC-induced PSC-MPP engrafted at a markedly higher level in NOD/SCID/IL-2 receptor γ chain–null (NSG) mice compared with cytokine-induced cells, and low-dose chemotherapy-based selection further increased engraftment. Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction were similar to levels achieved for cord blood–derived MPP and up to 20-fold higher than those achieved with hPSC-derived MPP engraftment. Our findings indicate that endothelial Notch ligands promote PSC-definitive hematopoiesis and production of long-term engrafting CD34+ cells, suggesting these ligands are critical for HSC emergence. PMID:25664855

  4. Comparative Analysis of the Hematopoietic Progenitor Cells from Placenta, Cord Blood, and Fetal Liver, Based on Their Immunophenotype

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    Maria D. Kuchma

    2015-01-01

    Full Text Available We have investigated the characteristics of human hematopoietic progenitor cells (HPCs with the CD34+CD45lowSSClow phenotype from full-term placental tissue (FTPT as compared to cord blood (CB and fetal liver (FL cells. We demonstrated the presence of cell subpopulations at various stages of the differentiation with such immunophenotypes as CD34+/lowCD45low/-, CD34++CD45low/-, CD34+++CD45low/-, CD34+/lowCD45hi, and CD34++CD45hi in both first trimester placental tissue (FiTPT and FTPT which implies their higher phenotypic heterogeneity compared to CB. HPCs of the FTPT origin expressed the CD90 antigen at a higher level compared to its expression by the CB HPCs and the CD133 antigen expression being at the same level in both cases. The HPCs compartment of FTPT versus CB contained higher number of myeloid and erythroid committed cells but lower number of myeloid and lymphoid ones compared to FL HPCs. HPCs of the FTPT and CB origin possess similar potentials for the multilineage differentiation in vitro and similar ratios of myeloid and erythroid progenitors among the committed cells. This observation suggests that the active hematopoiesis occurs in the FTPT. We obtained viable HPCs from cryopreserved placental tissue fragments allowing us to develop procedures for banking and testing of placenta-derived HPCs for clinical use.

  5. THE AGES OF TYPE Ia SUPERNOVA PROGENITORS

    International Nuclear Information System (INIS)

    Brandt, Timothy D.; Aubourg, Eric; Strauss, Michael A.; Tojeiro, Rita; Heavens, Alan; Jimenez, Raul

    2010-01-01

    Using light curves and host galaxy spectra of 101 Type Ia supernovae (SNe Ia) with redshift z ∼ 2.4 Gyr. We find that each channel contributes roughly half of the Type Ia rate in our reference sample. We also construct the average spectra of high-stretch and low-stretch SN Ia host galaxies, and find that the difference of these spectra looks like a main-sequence B star with nebular emission lines indicative of star formation. This supports our finding that there are two populations of SNe Ia, and indicates that the progenitors of high-stretch supernovae are at the least associated with very recent star formation in the last few tens of Myr. Our results provide valuable constraints for models of Type Ia progenitors and may help improve the calibration of SNe Ia as standard candles.

  6. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  7. Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

    Science.gov (United States)

    Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

    2016-03-21

    In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Observational Investigations of the Progenitors of Supernovae

    Science.gov (United States)

    Lyman, J. D.

    2014-03-01

    Supernovae (SNe) are the spectacular deaths of stars and have shaped the universe we see today. Their far-reaching influence affects the chemical and dynamical evolution of galaxies, star formation, neutron star and black hole formation, and they are largely responsible for most of the heavy elements that make up the universe, including around 90 per cent of the reader. They also provide laboratories of nuclear and particle physics far beyond what we can construct on Earth and act as probes of extreme density and energy. This thesis presents new research into understanding the nature of the progenitor systems of various types of SNe, as well as presenting results that will allow their study to be more productive in the future, through use of automated pipelines and methods to increase the science value of discovered SNe. An environmental study of two peculiar types of transients ('Calcium-rich' and '2002cx-like'), which may not be true SNe, reveals extremely different ages of the exploding systems that will constrain the current theoretical effort into discovering the progenitor systems. The GRB-SN 120422A/2012bz is investigated and found to be an extremely luminous and energetic SN, even amongst the infamously bright GRB-SNe. A method is presented that allows an accurate reconstruction of the bolometric light curve of a core-collapse SN, which relies on only two optical filter observations - this will hugely reduce the observational cost of constructing bolometric light curves, a tool of great importance when hoping to constrain the nature of a SN explosion and hence its progenitor. Finally, this method is utilised to construct the largest bolometric CCSN bolometric light curve sample to date, and these are analytically modelled to reveal population statistics of the explosions, thus informing on the nature of the progenitors.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  10. Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a.

    Science.gov (United States)

    Jackson, Jacob T; Shields, Benjamin J; Shi, Wei; Di Rago, Ladina; Metcalf, Donald; Nicola, Nicos A; McCormack, Matthew P

    2017-08-01

    The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of common lymphoid progenitors (CLPs) to lymphoid lineages. Here, we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation, due to a failure of progenitor expansion. In vitro, Hhex-null blast colonies were incapable of replating, implying a specific requirement for Hhex in immature progenitors. Transcriptome analysis of Hhex-null Lin - Sca + Kit + cells showed that Hhex deletion leads to derepression of polycomb repressive complex 2 (PRC2) and PRC1 target genes, including the Cdkn2a locus encoding the tumor suppressors p16 Ink 4 a and p19 Arf . Indeed, loss of Cdkn2a restored the capacity of Hhex-null blast colonies to generate myeloid progenitors in vitro, as well as hematopoietic reconstitution following myeloablation in vivo. Thus, HSCs require Hhex to promote PRC2-mediated Cdkn2a repression to enable continued self-renewal and response to hematopoietic stress. Stem Cells 2017;35:1948-1957. © 2017 AlphaMed Press.

  11. EVOLUTION OF PROGENITORS FOR ELECTRON CAPTURE SUPERNOVAE

    International Nuclear Information System (INIS)

    Takahashi, Koh; Umeda, Hideyuki; Yoshida, Takashi

    2013-01-01

    We provide progenitor models for electron capture supernovae (ECSNe) with detailed evolutionary calculation. We include minor electron capture nuclei using a large nuclear reaction network with updated reaction rates. For electron capture, the Coulomb correction of rates is treated and the contribution from neutron-rich isotopes is taken into account in each nuclear statistical equilibrium (NSE) composition. We calculate the evolution of the most massive super asymptotic giant branch stars and show that these stars undergo off-center carbon burning and form ONe cores at the center. These cores become heavier up to the critical mass of 1.367 M ☉ and keep contracting even after the initiation of O+Ne deflagration. Inclusion of minor electron capture nuclei causes convective URCA cooling during the contraction phase, but the effect on the progenitor evolution is small. On the other hand, electron capture by neutron-rich isotopes in the NSE region has a more significant effect. We discuss the uniqueness of the critical core mass for ECSNe and the effect of wind mass loss on the plausibility of our models for ECSN progenitors.

  12. Immunosuppression and tolerance after total lymphoid irradiation (TLI)

    International Nuclear Information System (INIS)

    Strober, S.; Gottlieb, M.; Slavin, S.; King, D.P.; Hoppe, R.T.; Fuks, Z.; Bieber, C.P.; Kaplan, H.S.

    1980-01-01

    The immunosuppressive effects of total lymphoid irradiation (TLI) in humans and in several species of inbred and outbred laboratory animals have been investigated. A unique property of TLI, the prevention of the graft vs. host disease, was used to induce transplantation tolerance in order to study the mechanism of altered immunity when the celluar basis of the TLI-induced immunosuppression was examined by means of the mixed lymphocyte response (MLR), no suppression of the MLR was observed when spleen cells from unirradiated or whole body-irradiated donors were used instead of donors given TLI. These results indicated that TLI induces a population of cells in the spleen that can nonspecifically suppress the MLR

  13. Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Yuhao Jiao

    2016-10-01

    Full Text Available Group 1 innate lymphoid cells (ILC comprise the natural killer (NK cells and ILC1 which reside within peripheral tissues. Several different ILC1 subsets have recently been characterised, however no unique markers to define these subsets have been identified. Whether ILC1 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 ILC 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 tumour immunosurveillance. Here, we review the diversity in the Group 1 ILC subsets with regards to their transcriptional regulation, localization, mobility and receptor expression and highlight the challenges in unraveling the individual functions of these different populations of cells.

  14. Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.

    Science.gov (United States)

    Xiong, Tingting; Turner, Jan-Eric

    2018-03-22

    Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.

  15. Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

    Science.gov (United States)

    Cosmi, Lorenzo; Liotta, Francesco; Maggi, Laura; Annunziato, Francesco

    2017-09-11

    The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.

  16. Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.

    Science.gov (United States)

    Zhang, Yi; Tang, Jun; Tian, Zhiqiang; van Velkinburgh, Jennifer C; Song, Jianxun; Wu, Yuzhang; Ni, Bing

    2016-09-02

    Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.

  17. Innate Lymphoid Cells: a new paradigm in immunology

    Science.gov (United States)

    Eberl, Gérard; Colonna, Marco; Di Santo, James P.; McKenzie, Andrew N.J.

    2016-01-01

    Summary Innate lymphoid cells (ILCs) are a growing family of immune cells that mirror the phenotypes and functions of T cells. However, in contrast to T cells, ILCs do not express acquired antigen receptors or undergo clonal selection and expansion when stimulated. Instead, ILCs react promptly to signals from infected or injured tissues and produce an array of secreted proteins termed cytokines that direct the developing immune response into one that is adapted to the original insult. The complex crosstalk between microenvironment, ILCs and adaptive immunity remains to be fully deciphered. Only by understanding these complex regulatory networks can the power of ILCs be controlled or unleashed to regulate or enhance immune responses in disease prevention and therapy. PMID:25999512

  18. Migration and Tissue Tropism of Innate Lymphoid Cells

    Science.gov (United States)

    Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo

    2016-01-01

    Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278

  19. Development and function of secondary and tertiary lymphoid organs in the small intestine and the colon

    Directory of Open Access Journals (Sweden)

    Manuela Buettner

    2016-09-01

    Full Text Available 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 programmed 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.

  20. 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

  1. 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.

  2. 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).

  3. Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency

    Directory of Open Access Journals (Sweden)

    Andrea Z. Tuckett

    2017-05-01

    Full Text Available Abstract Background Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice is feasible and facilitates the generation of functional T cells conferring protective immunity. Methods Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+, CD45.1+ and injected intravenously or intrathymically into both male and female, young or aged NOD-scid IL2rγnull recipients. The in vivo fate of injected cells was analyzed by bioluminescence imaging and flow cytometry of thymus- and spleen-derived T cell populations. In addition to T cell reconstitution, we evaluated mice for evidence of immune dysregulation based on diabetes development and graft-versus-host disease. T cell immunity following intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice was assessed in a B cell lymphoma model. Results Despite the small size of the thymic remnant in NOD-scid IL2rγnull mice, we were able to accomplish precise intrathymic delivery of hematopoietic stem and progenitor cells by ultrasound-guided injection. Thymic reconstitution following intrathymic injection of healthy allogeneic hematopoietic cells was most effective in young male recipients, indicating that even in the setting of severe immunodeficiency, sex and age are important variables for thymic function. Allogeneic T cells generated in intrathymically injected NOD-scid IL2rγnull mice displayed anti-lymphoma activity in vivo, but we found no evidence for severe auto/alloreactivity in T cell-producing NOD-scid IL2rγnull mice, suggesting that immune dysregulation is not a major concern

  4. Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells

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    Chow, Paik Wah [Biomedical Science Programme, School of Diagnostic & Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Abdul Muda Aziz, 50300 Kuala Lumpur, Wilayah Persekutuan (Malaysia); Toxicology Laboratory, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia); Abdul Hamid, Zariyantey, E-mail: zyantey@ukm.edu.my [Biomedical Science Programme, School of Diagnostic & Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Abdul Muda Aziz, 50300 Kuala Lumpur, Wilayah Persekutuan (Malaysia); Toxicology Laboratory, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia); Chan, Kok Meng [Environmental Health and Industrial Safety Programme, School of Diagnostic & Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Abdul Muda Aziz, 50300 Kuala Lumpur, Wilayah Persekutuan (Malaysia); Toxicology Laboratory, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia); Inayat-Hussain, Salmaan Hussain [Environmental Health and Industrial Safety Programme, School of Diagnostic & Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Abdul Muda Aziz, 50300 Kuala Lumpur, Wilayah Persekutuan (Malaysia); Rajab, Nor Fadilah [Biomedical Science Programme, School of Diagnostic & Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Abdul Muda Aziz, 50300 Kuala Lumpur, Wilayah Persekutuan (Malaysia); Toxicology Laboratory, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia)

    2015-04-01

    Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24 h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-forming unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e{sup +} cells but reduced the total counts of Sca-1{sup +}, CD11b{sup +}, Gr-1{sup +}, and CD45{sup +} cells at 7 and 12 μM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5 μM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12 μM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage. - Highlights: • We examine 1,4-BQ toxicity targeting mouse hematopoietic cell lineages. • 1,4-BQ induces concentration-dependent cytotoxicity in bone marrow (BM) cells. • 1,4-BQ shows lineage-related toxicity on hematopoietic stem and

  5. Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoietic stem and progenitor cells

    International Nuclear Information System (INIS)

    Chow, Paik Wah; Abdul Hamid, Zariyantey; Chan, Kok Meng; Inayat-Hussain, Salmaan Hussain; Rajab, Nor Fadilah

    2015-01-01

    Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are sensitive targets for benzene-induced hematotoxicity and leukemogenesis. The impact of benzene exposure on the complex microenvironment of HSCs and HPCs remains elusive. This study aims to investigate the mechanism linking benzene exposure to targeting HSCs and HPCs using phenotypic and clonogenic analyses. Mouse bone marrow (BM) cells were exposed ex vivo to the benzene metabolite, 1,4-benzoquinone (1,4-BQ), for 24 h. Expression of cellular surface antigens for HSC (Sca-1), myeloid (Gr-1, CD11b), and lymphoid (CD45, CD3e) populations were confirmed by flow cytometry. The clonogenicity of cells was studied using the colony-forming unit (CFU) assay for multilineage (CFU-GM and CFU-GEMM) and single-lineage (CFU-E, BFU-E, CFU-G, and CFU-M) progenitors. 1,4-BQ demonstrated concentration-dependent cytotoxicity in mouse BM cells. The percentage of apoptotic cells increased (p < 0.05) following 1,4-BQ exposure. Exposure to 1,4-BQ showed no significant effect on CD3e + cells but reduced the total counts of Sca-1 + , CD11b + , Gr-1 + , and CD45 + cells at 7 and 12 μM (p < 0.05). Furthermore, the CFU assay showed reduced (p < 0.05) clonogenicity in 1,4-BQ-treated cells. 1,4-BQ induced CFU-dependent cytotoxicity by significantly inhibiting colony growth for CFU-E, BFU-E, CFU-G, and CFU-M starting at a low concentration of exposure (5 μM); whereas for the CFU-GM and CFU-GEMM, the inhibition of colony growth was remarkable only at 7 and 12 μM of 1,4-BQ, respectively. Taken together, 1,4-BQ caused lineage-related cytotoxicity in mouse HPCs, demonstrating greater toxicity in single-lineage progenitors than in those of multi-lineage. - Highlights: • We examine 1,4-BQ toxicity targeting mouse hematopoietic cell lineages. • 1,4-BQ induces concentration-dependent cytotoxicity in bone marrow (BM) cells. • 1,4-BQ shows lineage-related toxicity on hematopoietic stem and progenitors. • 1,4-BQ

  6. Early Bronchus-Associated Lymphoid Tissue Lymphoma Diagnosed with Immunoglobulin Heavy Chain Molecular Testing

    Directory of Open Access Journals (Sweden)

    Pen Li

    2016-01-01

    Full Text Available When extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT, a low grade B-cell lymphoma, arises in the lung it is referred to as bronchus-associated lymphoid tissue (BALT lymphoma. We describe a patient with a history of Sjögren’s syndrome and rheumatoid arthritis with dyspnea and imaging consistent with lymphoid interstitial pneumonia (LIP. However, while histology and immunohistochemistry lacked definitive features of a lymphoma, immunoglobulin heavy chain (IgH polymerase chain reaction testing demonstrated B-cell monoclonality, consistent with an early BALT lymphoma.

  7. The effect of ionizing radiation on lipid metabolism in lymphoid cells

    International Nuclear Information System (INIS)

    Kolomiytseva, I.K.; Novoselova, E.G.; Kulagina, T.P.; Kuzin, A.M.

    1987-01-01

    Lipid metabolism was studied in lymphoid tissues of rats after whole body irradiation with doses producing damage of different degrees to lymphoid cells (4-10 Gy). The content of free cholesterol, cholesterol esters, and total phospholipids was determined in peripheral blood lymphocytes and thymocytes 1-2 h after exposure. Simultaneously, the rate of in vitro incorporation of 2 14 C-acetate into total lipids, phospholipids, and cholesterol of lymphoid cells was estimated. It was shown that exposure of rats to ionizing radiation caused activation of lipogenesis. Cholesterol synthesis was activated after a dose of 4 Gy and decreased with increasing dose. (author)

  8. Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Strober, S.; Fuks, Z.; Kaplan, H.S.

    1976-01-01

    Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2/sup d/ and H-2/sup b/, respectively). Infusion of 10 7 (C57BL/Ka x Balb/c)F 1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation

  9. Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors

    Directory of Open Access Journals (Sweden)

    Dongjun Lee

    2014-11-01

    Full Text Available Central to cellular proliferative, survival, and metabolic responses is the serine/threonine kinase mTOR, which is activated in many human cancers. mTOR is present in distinct complexes that are either modulated by AKT (mTORC1 or are upstream and regulatory of it (mTORC2. Governance of mTORC2 activity is poorly understood. Here, we report a transmembrane molecule in hematopoietic progenitor cells that physically interacts with and inhibits RICTOR, an essential component of mTORC2. Upstream of mTORC2 (UT2 negatively regulates mTORC2 enzymatic activity, reducing AKTS473, PKCα, and NDRG1 phosphorylation and increasing FOXO transcriptional activity in an mTORC2-dependent manner. Modulating UT2 levels altered animal survival in a T cell acute lymphoid leukemia (T-ALL model that is known to be mTORC2 sensitive. These studies identify an inhibitory component upstream of mTORC2 in hematopoietic cells that can reduce mortality from NOTCH-induced T-ALL. A transmembrane inhibitor of mTORC2 may provide an attractive target to affect this critical cell regulatory pathway.

  10. Reticular dysgenesis–associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress

    Science.gov (United States)

    Rissone, Alberto; Weinacht, Katja Gabriele; la Marca, Giancarlo; Bishop, Kevin; Giocaliere, Elisa; Jagadeesh, Jayashree; Felgentreff, Kerstin; Dobbs, Kerry; Al-Herz, Waleed; Jones, Marypat; Chandrasekharappa, Settara; Kirby, Martha; Wincovitch, Stephen; Simon, Karen Lyn; Itan, Yuval; DeVine, Alex; Schlaeger, Thorsten; Schambach, Axel; Sood, Raman

    2015-01-01

    Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in the energy homeostasis of all tissues. The AK2 isoenzyme is expressed in the mitochondrial intermembrane space and is mutated in reticular dysgenesis (RD), a rare form of severe combined immunodeficiency (SCID) in humans. RD is characterized by a maturation arrest in the myeloid and lymphoid lineages, leading to early onset, recurrent, and overwhelming infections. To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient. In zebrafish, Ak2 deficiency affected hematopoietic stem and progenitor cell (HSPC) development with increased oxidative stress and apoptosis. AK2-deficient iPSCs recapitulated the characteristic myeloid maturation arrest at the promyelocyte stage and demonstrated an increased AMP/ADP ratio, indicative of an energy-depleted adenine nucleotide profile. Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish and restored differentiation of AK2-deficient iPSCs into mature granulocytes. Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD. PMID:26150473

  11. The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.

    Science.gov (United States)

    Pitzonka, Laura; Ullas, Sumana; Chinnam, Meenalakshmi; Povinelli, Benjamin J; Fisher, Daniel T; Golding, Michelle; Appenheimer, Michelle M; Nemeth, Michael J; Evans, Sharon; Goodrich, David W

    2014-01-01

    Co-transcriptionally assembled ribonucleoprotein (RNP) complexes are critical for RNA processing and nuclear export. RNPs have been hypothesized to contribute to the regulation of coordinated gene expression, and defects in RNP biogenesis contribute to genome instability and disease. Despite the large number of RNPs and the importance of the molecular processes they mediate, the requirements for individual RNP complexes in mammalian development and tissue homeostasis are not well characterized. THO is an evolutionarily conserved, nuclear RNP complex that physically links nascent transcripts with the nuclear export apparatus. THO is essential for early mouse embryonic development, limiting characterization of the requirements for THO in adult tissues. To address this shortcoming, a mouse strain has been generated allowing inducible deletion of the Thoc1 gene which encodes an essential protein subunit of THO. Bone marrow reconstitution was used to generate mice in which Thoc1 deletion could be induced specifically in the hematopoietic system. We find that granulocyte macrophage progenitors have a cell autonomous requirement for Thoc1 to maintain cell growth and viability. Lymphoid lineages are not detectably affected by Thoc1 loss under the homeostatic conditions tested. Myeloid lineages may be more sensitive to Thoc1 loss due to their relatively high rate of proliferation and turnover.

  12. The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.

    Directory of Open Access Journals (Sweden)

    Laura Pitzonka

    Full Text Available Co-transcriptionally assembled ribonucleoprotein (RNP complexes are critical for RNA processing and nuclear export. RNPs have been hypothesized to contribute to the regulation of coordinated gene expression, and defects in RNP biogenesis contribute to genome instability and disease. Despite the large number of RNPs and the importance of the molecular processes they mediate, the requirements for individual RNP complexes in mammalian development and tissue homeostasis are not well characterized. THO is an evolutionarily conserved, nuclear RNP complex that physically links nascent transcripts with the nuclear export apparatus. THO is essential for early mouse embryonic development, limiting characterization of the requirements for THO in adult tissues. To address this shortcoming, a mouse strain has been generated allowing inducible deletion of the Thoc1 gene which encodes an essential protein subunit of THO. Bone marrow reconstitution was used to generate mice in which Thoc1 deletion could be induced specifically in the hematopoietic system. We find that granulocyte macrophage progenitors have a cell autonomous requirement for Thoc1 to maintain cell growth and viability. Lymphoid lineages are not detectably affected by Thoc1 loss under the homeostatic conditions tested. Myeloid lineages may be more sensitive to Thoc1 loss due to their relatively high rate of proliferation and turnover.

  13. Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

    Science.gov (United States)

    Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim

    2018-01-16

    Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. 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...

  15. Lymphotoxin organizes contributions to host defense and metabolic illness from innate lymphoid cells.

    Science.gov (United States)

    Upadhyay, Vaibhav; Fu, Yang-Xin

    2014-04-01

    The lymphotoxin (LT)-pathway is a unique constituent branch of the Tumor Necrosis Superfamily (TNFSF). Use of LT is a critical mechanism by which fetal innate lymphoid cells regulate lymphoid organogenesis. Within recent years, adult innate lymphoid cells have been discovered to utilize this same pathway to regulate IL-22 and IL-23 production for host defense. Notably, genetic studies have linked polymorphisms in the genes encoding LTα to several phenotypes contributing to metabolic syndrome. The role of the LT-pathway may lay the foundation for a bridge between host immune response, microbiota, and metabolic syndrome. The contribution of the LT-pathway to innate lymphoid cell function and metabolic syndrome will be visited in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Characterization of lymphoid cells in the blood of healthy adults: sequential immunological, cytochemical and cytokinetic studies

    International Nuclear Information System (INIS)

    Hirt, A.; Wagner, H.P.

    1980-01-01

    With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha-naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg-ANAE-cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE- cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E-sIg+ cells. The overall labeling index of the lymphoid cells examined was less than or equal to 0.2%

  17. Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma with a Nodular Opacity: Report of a Case.

    Science.gov (United States)

    Yoshino, Naoyuki; Hirata, Tomomi; Takeuchi, Chie; Usuda, Jitsuo; Hosone, Masaru

    2017-01-01

    Herein, we describe our experience in treating a case of primary pulmonary mucosa-associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old man was referred to our hospital. Computed tomography showed a nodular opacity measuring 20 mm in diameter with regular margins in segment 5 of the right middle lobe of the lung. Although the bronchoscopic brush cytology result was class III, the patient was tentatively diagnosed with suspected mucosa-associated lymphoid tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The pathological findings showed nodular proliferation of small to medium-sized, mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague follicles suggesting follicular colonization in some areas. The patient was diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. He has remained well to date, 23 months after surgery, without evidence of recurrence.

  18. Spectrum of lymphoid hyperplasia: colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Ell, S.R.; Frank, P.H.

    1981-10-15

    The radiographic pattern of nodular lymphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases.

  19. Characterization of membranous (M) cells in normal feline conjunctiva-associated lymphoid tissue (CALT).

    Science.gov (United States)

    Giuliano, Elizabeth A; Finn, Kevin

    2011-09-01

    To characterize conjunctival lymphoid nodules obtained from the nictitans of healthy cats to determine if the follicle-associated epithelium (FAE) of conjunctiva-associated lymphoid tissue (CALT) in this species contains membranous (M)-cells analogous to those described in other regions of mucosa-associated lymphoid tissue (MALT). Lymphoid follicles from nictitan bulbar surfaces of 10 healthy cats (20 eyes total) were examined. Nictitans from five cats were harvested immediately post-mortem and a minimum of 12 lymphoid nodules from each third eyelid were isolated using a Zeiss operating microscope. At least three lymphoid follicles from each eye were examined using light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) using standard fixation and embedding protocols. Nictitan-lymphoid follicles from another five healthy cats were processed for immunohistochemistry to characterize the distribution of T- and B-lymphocytes present beneath the FAE. The FAE overlying CALT from 10 healthy cats demonstrated morphology characteristic of M-cells including attenuated apical cell surface with blunted microvilli and microfolds, invaginated basolateral membrane forming a cytoplasmic pocket, and diminished distance between the apical and pocket membrane. Immunohistochemistry of lymphoid tissue subtending the FAE demonstrated B-cell dependent regions in the germinal centers surrounded by T-cell dependent interfollicular zones. Healthy feline CALT contains morphologic features analogous to those described in other regions of MALT. Documentation of feline conjunctival M-cells is of clinical relevance in the study of primary infectious, allergic, and autoimmune ocular diseases, as well as a potential means of vaccination or drug delivery. © 2011 American College of Veterinary Ophthalmologists.

  20. Metabolic and physiologic studies of nonimmune lymphoid cells cytotoxic for fibroblastic cells in vitro

    International Nuclear Information System (INIS)

    Mayhew, E.; Bennett, M.

    1974-01-01

    An in vitro reaction between mouse lymphoid cells and target fibroblastic cells in wells of microtest plates, which appears to simulate the in vivo rejection of hemopoietic allografts, has been analyzed for metabolic and physiologic requirements. Protein synthesis was required for only the first few hours of culture. Inhibition of RNA synthesis and alteration of cell surface charge with various agents were without obvious effects. Metabolic slowing at 4 0 C or deviation of the pH of the culture medium suppressed the reaction. Thymus cells, which are not cytotoxic in this system, significantly but not completely inhibited the cytotoxicity of lymph node cells. Antiserum directed against target cells specifically protected them from the cytotoxic lymphoid cells in the absence of complement. Precursors of cytotoxic lymphoid cells were radiosensitive, unlike the cytotoxic cells themselves. BALB/c anti-C57BL/6 spleen cell serum and 89 Sr both are able to prevent rejection of marrow allografts in vivo. Lymphoid cells incubated with this antiserum plus complement lost much of their cytotoxicity but were still effective at high ratios of aggressor to target cells. Lymphoid cells of mice treated with 89 Sr were effectively cytotoxic but lost practically all of their cytotoxicity after incubation with the antiserum plus complement. Thus, it appears that this reaction detects two different cytotoxic lymphoid cells, either of which can function in vitro. Both cell types may need to cooperate in vivo during marrow allograft rejections

  1. 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. Copyright © 2015 by The American Association of Immunologists, Inc.

  2. Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human 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 in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

  3. Immunophenotype of cells within cervine rectoanal mucosa-associated lymphoid tissue and mesenteric lymph nodes.

    Science.gov (United States)

    Dagleish, M P; Finlayson, J; Steele, P J; Pang, Y; Hamilton, S; Eaton, S L; Sales, J; González, L; Chianini, F

    2012-05-01

    Rectoanal mucosa-associated lymphoid tissue (RAMALT) is a part of the lymphoid system that can be sampled easily in live animals, especially ruminants. RAMALT biopsy is useful for the diagnosis of transmissible spongiform encephalopathies, including scrapie in sheep and goats and chronic wasting disease (CWD) in cervids. Diagnosis is reliant on detection of abnormal prion protein (PrP(d)), which is associated with lymphoid follicles. For enzyme linked immunosorbent assays (ELISAs) detecting PrP(d) it is necessary to ensure that lymphoid follicles are present in biopsy samples to avoid false-negative results. Monoclonal antibodies known to recognize specific immune cell subsets present in lymphoid tissues of sheep were tested for cross-reactivity with cervine RAMALT and mesenteric lymph nodes (MLNs) preserved in zinc salts fixative. The distribution of cells expressing CD3, CD4, CD79, CD21 and class II molecules of the major histocompatibility complex was determined in these tissues. Cells of each immunophenotype had similar distributions in RAMALT and MLNs and these distributions were similar to those reported previously for sheep and cattle. The identification and validation of cervine lymphoid follicle cell markers (CD79 and CD21) may allow reduction in false-negative results during diagnosis of CWD by ELISA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Tertiary Lymphoid Structures in Cancer: Drivers of Antitumor Immunity, Immunosuppression, or Bystander Sentinels in Disease?

    Science.gov (United States)

    Colbeck, Emily Jayne; Ager, Ann; Gallimore, Awen; Jones, Gareth Wyn

    2017-01-01

    Secondary lymphoid organs are integral to initiation and execution of adaptive immune responses. These organs provide a setting for interactions between antigen-specific lymphocytes and antigen-presenting cells recruited from local infected or inflamed tissues. Secondary lymphoid organs develop as a part of a genetically preprogrammed process during embryogenesis. However, organogenesis of secondary lymphoid tissues can also be recapitulated in adulthood during de novo lymphoid neogenesis of tertiary lymphoid structures (TLSs). These ectopic lymphoid-like structures form in the inflamed tissues afflicted by various pathological conditions, including cancer, autoimmunity, infection, or allograft rejection. Studies are beginning to shed light on the function of such structures in different disease settings, raising important questions regarding their contribution to progression or resolution of disease. Data show an association between the tumor-associated TLSs and a favorable prognosis in various types of human cancer, attracting the speculation that TLSs support effective local antitumor immune responses. However, definitive evidence for the role for TLSs in fostering immune responses in vivo are lacking, with current data remaining largely correlative by nature. In fact, some more recent studies have even demonstrated an immunosuppressive, tumor-promoting role for cancer-associated TLSs. In this review, we will discuss what is known about the development of cancer-associated TLSs and the current understanding of their potential role in the antitumor immune response. PMID:29312327

  5. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Lavik, Erin B

    2005-01-01

    To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs.......To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs....

  6. Treatment of experimental myasthenia gravis with total lymphoid irradiation

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  7. Clinical drawbacks of total lymphoid irradiation: the cons

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  8. Role of innate lymphoid cells in obesity and metabolic disease

    Science.gov (United States)

    Saetang, Jirakrit; Sangkhathat, Surasak

    2018-01-01

    The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853

  9. Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor

    Science.gov (United States)

    Li, Shiyang; Bostick, John W.; Zhou, Liang

    2018-01-01

    With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs) represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer cells, T-bet+ Eomes− group 1 ILCs, GATA3+ group 2 ILCs, RORγt+ group 3 ILCs, and newly identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin) at the interface of host–environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs. The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor, best known to mediate the effects of xenobiotic environmental toxins and endogenous microbial and dietary metabolites. Here, we review recent progresses regarding Ahr function in ILCs. We focus on the Ahr-mediated cross talk between ILCs and other immune/non-immune cells in host tissues especially in the gut. We discuss the molecular mechanisms of the action of Ahr expression and activity in regulation of ILCs in immunity and inflammation, and the interaction between Ahr and other pathways/transcription factors in ILC development and function with their implication in disease. PMID:29354125

  10. Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor

    Directory of Open Access Journals (Sweden)

    Shiyang Li

    2018-01-01

    Full Text Available With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer cells, T-bet+ Eomes− group 1 ILCs, GATA3+ group 2 ILCs, RORγt+ group 3 ILCs, and newly identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin at the interface of host–environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs. The aryl hydrocarbon receptor (Ahr is a ligand-dependent transcription factor, best known to mediate the effects of xenobiotic environmental toxins and endogenous microbial and dietary metabolites. Here, we review recent progresses regarding Ahr function in ILCs. We focus on the Ahr-mediated cross talk between ILCs and other immune/non-immune cells in host tissues especially in the gut. We discuss the molecular mechanisms of the action of Ahr expression and activity in regulation of ILCs in immunity and inflammation, and the interaction between Ahr and other pathways/transcription factors in ILC development and function with their implication in disease.

  11. Innate lymphoid cells at the interface between obesity and asthma.

    Science.gov (United States)

    Everaere, Laetitia; Ait Yahia, Saliha; Bouté, Mélodie; Audousset, Camille; Chenivesse, Cécile; Tsicopoulos, Anne

    2018-01-01

    Obesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases, in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided into three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts. However, unlike T helper cells, ILCs do not express antigen-specific receptors, but respond to damage-induced signals. ILCs have been found in target tissues of both diseases, and data have implicated these cells in the pathogenesis of both diseases. In particular group 2 ILCs (ILC2) are activated in both the adipose and lung tissues under the effect of interleukin-33 and interleukin-25 expression. However, counter-intuitively to the well-known association between obesity and asthma, ILC2 are beneficial for obesity but deleterious for asthma. This review will examine the roles of ILCs in each disease and recent data highlighting ILCs as a putative link between obesity and asthma. © 2017 John Wiley & Sons Ltd.

  12. Kidney allograft survival in dogs treated with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-01-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients

  13. 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.

  14. CT appearances of mucosa-associated lymphoid tissue (MALT) lymphoma

    International Nuclear Information System (INIS)

    Kessar, P.; Norton, A.; Rohatiner, A.Z.S.; Lister, T.A.; Reznek, R.H.

    1999-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade lymphoma that differs from high-grade non-Hodgkin lymphoma both clinically and histologically. The CT appearances of MALT lymphoma are described. Of 40 patients referred with biopsy-proven MALT lymphoma, only seven had not had gastrectomy or chemotherapy prior to CT examination. The CT scans of these seven cases were analysed for the degree and extent of gastric wall thickening, enlargement of abdominal and extra-abdominal lymph nodes, and presence of extranodal disease. In all patients the stomach was distended with oral contrast medium and scans performed at narrow collimation, after intravenous administration of 20 mg hyoscine butylbromide. In six patients focal thickening of the gastric wall was 1 cm or less. One patient had thickening of over 4 cm. There was no enlargement of abdominal or extra-abdominal lymph nodes or extension to adjacent organs. Thus on CT, at presentation, MALT lymphoma results in minimal gastric wall thickening, unlike high-grade non-Hodgkin lymphoma, which typically causes bulky gastric disease, nodal enlargement and extension into adjacent organs. CT is therefore of limited value in monitoring response to treatment. With disease greater than minimal thickening, transformation to a higher grade should be considered. (orig.)

  15. Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

    Science.gov (United States)

    Rubio, Carlos A; DE Petris, Giovanni; Puppa, Giacomo

    2018-02-01

    In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. CT findings of pulmonary mucosa-associated lymphoid tissue lymphoma

    International Nuclear Information System (INIS)

    Zhang Weidong; Guan Yubao; Li Chuanxing; Wu Peihong

    2010-01-01

    Objective: To study the CT findings of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: The CT examinations of 12 patients with pathologically proven pulmonary MALT lymphoma were reviewed retrospectively. Evaluated imaging findings included number, distribution, shape, attenuation and other associated findings of each lesion were evaluated. Results: Thirty-two pulmonary lesions, including consolidations, masses, nodules and lesions with ground glass attenuation, were identified in 12 patients. Multiple lesions were founded in 10 of 12 patients and solitary lesion in 2 patients. Multiple lesions found in one lung in 2 patients, and multiple lesions found in both lungs in 8 patients. Ten cases demonstrated 21 consolidation lesions with air bronchogram, and one of the ten cases demonstrated two lesions with airway dilatation. Three cases demonstrated 5 masses or nodular lesions, 3 of these 5 lesions showed air bronchogram. Two cases demonstrated 6 ground glass attenuation lesions. One case showed mediastinal and hilar lymphadenopathy. Conclusion: Pulmonary MALT lymphoma usually appears as multiple bilateral consolidations, masses, nodules with air bronchogram or lesions with ground- glass attenuation at CT imaging. The imaging findings described above and with an indolent clinical course may suggest the diagnosis of pulmonary MALT lymphoma. (authors)

  17. Innate lymphoid cells and their role in immune response regulation

    Directory of Open Access Journals (Sweden)

    Bibiana Patricia Ruiz-Sánchez

    2017-10-01

    Full Text Available Innate lymphoid cells (ILCs are lymphocytes lacking antigen recognition receptors and become activated in response to cytokines and through microbe-associated molecular pattern (MAMP receptors. ILCs are found mainly in mucosal tissues and participate in the immune response against infections and in chronic inflammatory conditions. ILCs are divided in ILC-1, ILC-2 and ILC-3, and these cells have analogue functions to those of immune adaptive response lymphocytes Th1, Th2 and Th17. ILC-1 express T-bet, produce IFNγ, protect against infections with intracellular microorganisms and are related to inflammatory bowel disease immunopathology. ILC-2 express GATA3, produce IL-4, IL-5, IL-13 and amphiregulin, protect against parasitic infections and related to allergy and obesity immunopathology. ILC-3 express ROR(γt, produce IL-17 and IL-22, protect against fungal infections and contribute to tolerance to intestinal microbiota and intestinal repair. They are related to inflammatory bowel disease and psoriasis immunopathology. In general terms, ILCs maintain homeostasis and coadjuvate in the protection against infections.

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

    Directory of Open Access Journals (Sweden)

    E. L. Nazarova

    2014-01-01

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

  19. Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

    Directory of Open Access Journals (Sweden)

    Meike Mitsdoerffer

    2016-10-01

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

  20. Selective uptake of boronophenylalanine by glioma stem/progenitor cells

    International Nuclear Information System (INIS)

    Sun, Ting; Zhou, Youxin; Xie, Xueshun; Chen, Guilin; Li, Bin; Wei, Yongxin; Chen, Jinming; Huang, Qiang; Du, Ziwei

    2012-01-01

    The success of boron neutron capture therapy (BNCT) depends on the amount of boron in cells and the tumor/blood and tumor/(normal tissue) boron concentration ratios. For the first time, measurements of boron uptake in both stem/progenitor and differentiated glioma cells were performed along with measurements of boron biodistribution in suitable animal models. In glioma stem/progenitor cells, the selective accumulation of boronophenylalanine (BPA) was lower, and retention of boron after BPA removal was longer than in differentiated glioma cells in vitro. However, boron biodistribution was not statistically significantly different in mice with xenografts. - Highlights: ► Uptake of BPA was analyzed in stem/progenitor and differentiated glioma cells. ► Selective accumulation of BPA was lower in glioma stem/progenitor cells. ► Retention of boron after BPA removal was longer in glioma stem/progenitor cells. ► Boron biodistribution was not statistically different in mice with xenografts.

  1. Impairment of circulating endothelial progenitors in Down syndrome

    Directory of Open Access Journals (Sweden)

    Costa Valerio

    2010-09-01

    Full Text Available Abstract Background Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions Our data provide evidences for a reduced number and altered

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

    Science.gov (United States)

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

    1997-01-01

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

  3. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients.

    Science.gov (United States)

    Diaz, Alba; Alós, Llúcia; León, Agathe; Mozos, Anna; Caballero, Miguel; Martinez, Antonio; Plana, Montserrat; Gallart, Teresa; Gil, Cristina; Leal, Manuel; Gatell, Jose M; García, Felipe

    2010-08-24

    The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. Tonsillar biopsies were performed in seven antiretroviral-naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor-sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue.

  4. Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice.

    Science.gov (United States)

    Lohrberg, Melanie; Pabst, Reinhard; Wilting, Jörg

    2018-01-25

    The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology. Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics. NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

  5. Group 1 innate lymphoid cells in Toxoplasma gondii infection.

    Science.gov (United States)

    Dunay, I R; Diefenbach, A

    2018-02-01

    Innate lymphoid cells (ILCs) are a group of lymphocytes that carry out important functions in immunity to infections and in organ homeostasis at epithelial barrier surfaces. ILCs are innate immune cells that provide an early source of cytokines to initiate immune responses against pathogens. Cytotoxic ILCs (i.e. conventional (c)NK cells) and several subsets of helper-like ILCs are the major branches of the ILC family. Conventional NK cells and group 1 ILCs share several characteristics such as surface receptors and the ability to produce IFN-γ upon activation, but they differ in their developmental paths and in their dependence on specific transcription factors. Infection of mice with the intracellular parasite Toxoplasma gondii is followed by a strong Th1-mediated immune response. Previous studies indicate that NK1.1 + cells contribute to the production of IFN-γ and TNF and cytotoxicity during acute T. gondii infection. Upon oral infection, the parasite infects intestinal enterocytes, and within the lamina propria, innate immune responses lead to initial parasite control although the infection disseminates widely and persists long-term in immune privileged sites despite adaptive immunity. Upon parasite entry into the small intestine, during the acute stage, ILC1 produce high levels of IFN-γ and TNF protecting barrier surfaces, thus essentially contributing to early parasite control. We will discuss here the role of innate lymphocytes during T. gondii infection in the context of the only recently appreciated diversity of ILC subsets. © 2018 John Wiley & Sons Ltd.

  6. Scrapie-specific pathology of sheep lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

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

  7. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    Gelovani, Juri G.

    2008-01-01

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  8. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo

    2017-02-22

    For many years, myocardial tissue has been considered terminally differentiated and, thus, incapable of regenerating. Recent studies have shown, instead, that cardiomyocytes, at least in part, are slowly substituted by new cells originating by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient. The protocol here reported describes how from auricles a population of multipotent, cardiogenic cells can be isolated, cultured, and differentiated. Further studies are needed to fully exploit this cell population, but, sampling auricles, it could be possible to treat cardiac patients using their own cells circumventing rejection or organ shortage limitations.

  9. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  10. A COMPREHENSIVE PROGENITOR MODEL FOR SNe Ia

    International Nuclear Information System (INIS)

    Meng, X.; Yang, W.

    2010-01-01

    Although the nature of the progenitor of Type Ia supernovae (SNe Ia) is still unclear, the single-degenerate (SD) channel for the progenitor is currently accepted, in which a carbon-oxygen white dwarf (CO WD) accretes hydrogen-rich material from its companion, increases its mass to the Chandrasekhar mass limit, and then explodes as an SN Ia. The companion may be a main sequence or a slightly evolved star (WD + MS), or a red giant star (WD + RG). Incorporating the effect of mass stripping and accretion-disk instability on the evolution of the WD binary, we carried out binary stellar evolution calculations for more than 1600 close WD binaries. As a result, the initial parameter spaces for SNe Ia are presented in an orbital period-secondary mass (log P i , M i 2 ) plane. We confirmed that in a WD + MS system, the initial companion leading to SNe Ia may have mass from 1 M sun to 5 M sun . The initial WD mass for SNe Ia from WD + MS channel is as low as 0.565 M sun , while the lowest WD mass from the WD + RG channel is 1.0 M sun . Adopting the above results, we studied the birth rate of SNe Ia via a binary population synthesis approach. We found that the Galactic SNe Ia birth rate from SD model is (2.55-2.9) x 10 -3 yr -1 (including WD + He star channel), which is slightly smaller than that from observation. If a single starburst is assumed, the distribution of the delay time of SNe Ia from the SD model may be a weak bimodality, where WD + He channel contributes to SNe Ia with delay time shorter than 10 8 yr and WD + RG channel to those with age longer than 6 Gyr.

  11. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    Energy Technology Data Exchange (ETDEWEB)

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G. [Instituto de Astrofísica de La Plata (Argentina); Kuncarayakti, Hanindyo [Millennium Institute of Astrophysics (MAS), Casilla 36-D, Santiago (Chile); Maeda, Keiichi; Nomoto, Ken’ichi, E-mail: gaston@fcaglp.unlp.edu.ar [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan)

    2015-10-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M{sub ⊙} and the radius was 30–50 R{sub ⊙}, which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion.

  12. Ionizing radiation induces apoptosis in hematopoietic stem and progenitor cells

    International Nuclear Information System (INIS)

    Meng, A.; Zhou, D.; Geiger, H.; Zant, G.V.

    2003-01-01

    The aims of this study was to determine if ionizing radiation (IR) induces apoptosis in hematopoietic stem (HSC) and progenitor cells. Lin-cells were isolated from mouse bone marrow (BM) and pretreated with vehicle or 100 μM z-VAD 1 h prior to exposure to 4 Gy IR. The apoptotic and/or necrotic responses of these cells to IR were analyzed by measuring the annexin V and/or 7-AAD staining in HSC and progenitor populations using flow cytometry, and hematopoietic function of these cells was determined by CAFC assay. Exposure of Lin-cells to IR selectively decreased the numbers of HSC and progenitors in association with an increase in apoptosis in a time-dependent manner. Pretreatment of Lin- cells with z-VAD significantly inhibited IR-induced apoptosis and the decrease in the numbers of HSC and progenitors. However, IR alone or in combination with z-VAD did not lead to a significant increase in necrotic cell death in either HSC or progenitors. In addition, pretreatment of BM cells with z-VAD significantly attenuated IR-induced reduction in the frequencies of day-7, -28 and -35 CAFC. Exposure of HSC and progenitors to IR induces apoptosis. The induction of HSC and progenitor apoptosis contributes to IR-induced suppression of their hematopoietic function

  13. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    International Nuclear Information System (INIS)

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G.; Kuncarayakti, Hanindyo; Maeda, Keiichi; Nomoto, Ken’ichi

    2015-01-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M ⊙ and the radius was 30–50 R ⊙ , which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion

  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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 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.

  16. 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.

  17. The enigma of the lower gut-associated lymphoid tissue (GALT).

    Science.gov (United States)

    Butler, John E; Sinkora, Marek

    2013-08-01

    Artiodactyls possess GALT that appears in fetal life and is located at the extreme end of the ileum. These IPP contain mostly B cells and involute early in postnatal life. Rabbits have a similarly located lymphoid organ, called the sacculus rotundus. Studies in sheep and rabbits have led to the concept that the lower hindgut GALT represents primary lymphoid tissue for B cells and is necessary for normal B cell development, analogous to the bursa of Fabricius. This review traces the history of the observations and theories that have led to the existing concept concerning the role of lower GALT. We then review recent data from piglets with resected IPP that challenges the concept that the IPP is primary B cell lymphoid tissue and that artiodactyls and rabbits are members of the GALT group in the same context as gallinaceous birds. Eliminating the IPP as the primary lymphoid tissue for B cells leads to the hypothesis that the IPP acts as first-responder mucosal lymphoid tissue.

  18. 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.

  19. The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.

    Science.gov (United States)

    Mastropasqua, Rodolfo; Agnifili, Luca; Fasanella, Vincenzo; Nubile, Mario; Gnama, Agbeanda A; Falconio, Gennaro; Perri, Paolo; Di Staso, Silvio; Mariotti, Cesare

    2017-08-01

    Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

  20. Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yankee, Thomas M; Solow, Sasha A; Draves, Kevin D; Clark, Edward A

    2003-01-01

    Adapter proteins play a critical role in regulating signals triggered by Ag receptor cross-linking. These small molecules link receptor proximal events with downstream signaling pathways. In this study, we explore the expression and function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related adaptor downstream of Shc adapter protein in human B cells. GrpL is expressed in naive B cells and is down-regulated following B cell Ag receptor ligation. By contrast, germinal center and memory B cells express little or no GrpL. Using human B cell lines, we detected constitutive interactions between GrpL and B cell linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa, hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2 domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular signal-related kinase and p38 mitogen-activated protein kinase phosphorylation. Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor-mediated signaling events.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  3. Pathological and therapeutic roles of innate lymphoid cells in diverse diseases.

    Science.gov (United States)

    Kim, Jisu; Kim, Geon; Min, Hyeyoung

    2017-11-01

    Innate lymphoid cells (ILCs) are a recently defined type of innate-immunity cells that belong to the lymphoid lineage and have lymphoid morphology but do not express an antigen-specific B cell or T-cell receptor. ILCs regulate immune functions prior to the formation of adaptive immunity and exert effector functions through a cytokine release. ILCs have been classified into three groups according to the transcription factors that regulate their development and function and the effector cytokines they produce. Of note, ILCs resemble T helper (Th) cells, such as Th1, Th2, and Th17 cells, and show a similar dependence on transcription factors and distinct cytokine production. Despite their short history in immunology, ILCs have received much attention, and numerous studies have revealed biological functions of ILCs including host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. Here, we describe recent findings about the roles of ILCs in the pathogenesis of various diseases and potential therapeutic targets.

  4. 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...... response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...

  5. Twin Rectal Tonsils Mimicking Carcinoid or Mucosa-Associated Lymphoid Tissue Lymphoma.

    Science.gov (United States)

    Takehara, Masanori; Muguruma, Naoki; Kitamura, Shinji; Kimura, Tetsuo; Okamoto, Koichi; Miyamoto, Hiroshi; Bando, Yoshimi; Takayama, Tetsuji

    2017-09-01

    The rectal tonsil is a rare polypoid lesion exclusively found in the rectum and is considered a reactive proliferation of the lymphoid tissue. Although this lesion is benign, we recommend that it should be differentiated from carcinoid or polypoid type of mucosa-associated lymphoid tissue lymphomas, based on gross findings. In this case report, we describe a case of rectal lesions with a unique appearance in a 41-year-old man. Colonoscopy revealed two 5-mm-sized nodules located opposite from each other on the left and right sides of the lower rectum. Endoscopic mucosal resection was conducted. Histopathologically, both lesions were mainly located in the submucosa and consisted of prominent lymphoid follicles with germinal centers of various sizes. No immunoreactivity of Bcl-2 was seen in the germinal centers. Immunohistochemical staining for kappa and lambda light chains revealed a polyclonal pattern. Therefore, these lesions were diagnosed as rectal tonsils.

  6. Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia.

    Science.gov (United States)

    Tommola, Päivi; Bützow, Ralf; Unkila-Kallio, Leila; Paavonen, Jorma; Meri, Seppo

    2015-04-01

    Localized provoked vulvodynia (LPV) may have inflammatory etiology. We wanted to find out whether the cell-mediated immune system becomes activated in the vestibular mucosa in LPV. This was a controlled cross-sectional study. Vestibular mucosal specimens were obtained from 27 patients with severe LPV and 15 controls. Detailed clinical history of the patients was obtained. For immunohistochemistry, antibodies against CD3 (T cells), CD20 (B cells), IgA (mucosal plasma cells), CD163 (dendritic cells [DCs]), CD68 (macrophages), and CD117 (mast cells) were employed. Mann-Whitney U test and χ(2) test were used for statistical analyses. More B lymphocytes and mature mucosal IgA-plasma cells were found in patients than in controls (P associated lymphoid tissue analogous to mucosa-associated lymphoid tissue. Vestibule-associated lymphoid tissue may emerge as a response to local infection or inflammation in LPV. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  8. 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.

  9. A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation.

    Science.gov (United States)

    Nestorowa, Sonia; Hamey, Fiona K; Pijuan Sala, Blanca; Diamanti, Evangelia; Shepherd, Mairi; Laurenti, Elisa; Wilson, Nicola K; Kent, David G; Göttgens, Berthold

    2016-08-25

    Maintenance of the blood system requires balanced cell fate decisions by hematopoietic stem and progenitor cells (HSPCs). Because cell fate choices are executed at the individual cell level, new single-cell profiling technologies offer exciting possibilities for mapping the dynamic molecular changes underlying HSPC differentiation. Here, we have used single-cell RNA sequencing to profile more than 1600 single HSPCs, and deep sequencing has enabled detection of an average of 6558 protein-coding genes per cell. Index sorting, in combination with broad sorting gates, allowed us to retrospectively assign cells to 12 commonly sorted HSPC phenotypes while also capturing intermediate cells typically excluded by conventional gating. We further show that independently generated single-cell data sets can be projected onto the single-cell resolution expression map to directly compare data from multiple groups and to build and refine new hypotheses. Reconstruction of differentiation trajectories reveals dynamic expression changes associated with early lymphoid, erythroid, and granulocyte-macrophage differentiation. The latter two trajectories were characterized by common upregulation of cell cycle and oxidative phosphorylation transcriptional programs. By using external spike-in controls, we estimate absolute messenger RNA (mRNA) levels per cell, showing for the first time that despite a general reduction in total mRNA, a subset of genes shows higher expression levels in immature stem cells consistent with active maintenance of the stem-cell state. Finally, we report the development of an intuitive Web interface as a new community resource to permit visualization of gene expression in HSPCs at single-cell resolution for any gene of choice. © 2016 by The American Society of Hematology.

  10. MRI of idiopathic orbital inflammation and lymphoid disease with lesions in extraocular muscle

    International Nuclear Information System (INIS)

    Matsuda, Chiharu; Kotake, Fumio; Kawanishi, Masayuki; Saito, Kazuhiro; Abe, Kimihiko

    2004-01-01

    Of the disorders accompanied by hypertrophy of the extraocular muscles, differentiating between idiopathic orbital inflammation and malignant lymphoma is difficult but important to treatment and prognosis. In this study using MRI, shape, signal intensity, and enhancement effects were compared between idiopathic orbital inflammation and lymphoproliferative lesions. The subjects were 27 patients (8 with idiopathic orbital inflammation, 1 with reactive lymphoid hyperplasia, 3 with atypical lymphoid hyperplasia, and 15 with malignant lymphoma) and 10 normal controls. The evaluation items were: thickness of extraocular muscles, number of extraocular muscles involved signal intensity of extraocular muscles, and enhancement effects on extraocular muscles. When compared to control subjects (p<0.05) the attachment portion of extraocular muscles were significantly thicker in the patients with idiopathic orbital inflammation, atypical lymphoid hyperplasia, or malignant lymphoma; the most marked hypertrophy was observed in patients with malignant lymphoma. The number of extraocular muscles involved was 1.5 (mean) in the patients with idiopathic orbital inflammation, 1 in the patient with reactive lymphoid hyperplasia, 1.7 (mean) in the patients with atypical lymphoid hyperplasia, and 5.1 (mean) in those with malignant lymphoma. The signal intensity ratio on T1W-images did not significantly differ between the patients and controls for all the disorders investigated. Signal intensity ratio on T2W-images significantly differed between patients with atypical lymphoid hyperplasia or malignant lymphoma and the controls (p<0.05) but not between patients with idiopathic orbital inflammation and controls. Signal intensity ratio after contrast enhancement differed significantly only between patients with idiopathic orbital inflammation and controls (p<0.05). (author)

  11. Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2012-01-01

    Type 2 innate lymphoid cells (ILC2s) are members of an ILCfamily, which contains NKcells and Ror?t+ ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL-17 and IL-22. ILC2s are dedicated to the production of IL-5 and IL-13 and, as such, ILC2s provide an early and

  12. Regulation of Cytokine Secretion in Human CD127(+) LTi-like Innate Lymphoid Cells by Toll-like Receptor 2

    NARCIS (Netherlands)

    Crellin, Natasha K.; Trifari, Sara; Kaplan, Charles D.; Satoh-Takayama, Naoko; Di Santo, James P.; Spits, Hergen

    2010-01-01

    Lymphoid tissue inducer cells are members of an emerging family of innate lymphoid cells (ILC). Although these cells were originally reported to produce cytokines such as interleukin-17 (IL-17) and IL-22, we demonstrate here that human CD127(+)RORC(+) and CD56(+)CD127(+) LTi-like ILC also express

  13. PU.1 is essential for CD11c expression in CD8(+/CD8(- lymphoid and monocyte-derived dendritic cells during GM-CSF or FLT3L-induced differentiation.

    Directory of Open Access Journals (Sweden)

    Xue-Jun Zhu

    Full Text Available Dendritic cells (DCs regulate innate and acquired immunity through their roles as antigen-presenting cells. Specific subsets of mature DCs, including monocyte-derived and lymphoid-derived DCs, can be distinguished based on distinct immunophenotypes and functional properties. The leukocyte integrin, CD11c, is considered a specific marker for DCs and it is expressed by all DC subsets. We created a strain of mice in which DCs and their progenitors could be lineage traced based on activity of the CD11c proximal promoter. Surprisingly, we observed levels of CD11c promoter activity that were similar in DCs and in other mature leukocytes, including monocytes, granulocytes, and lymphocytes. We sought to identify DNA elements and transcription factors that regulate DC-associated expression of CD11c. The ets transcription factor, PU.1, is a key regulator of DC development, and expression of PU.1 varies in different DC subsets. GM-CSF increased monocyte-derived DCs in mice and from mouse bone marrow cultured in vitro, but it did not increase CD8(+ lymphoid-derived DCs or B220(+ plasmacytoid DCs. FLT3L increased both monocyte-derived DCs and lymphoid-derived DCs from mouse bone marrow cultured in vitro. GM-CSF increased the 5.3 Kb CD11c proximal promoter activity in monocyte-derived DCs and CD8(+ lymphoid-derived DCs, but not in B220(+ plasmacytoid DCs. In contrast, FLT3L increased the CD11c proximal promoter activity in both monocyte-derived DCs and B220(+ plasmacytoid DCs. We used shRNA gene knockdown and chromatin immunoprecipitation to demonstrate that PU.1 is required for the effects of GM-CSF or FLT3L on monocyte-derived DCs. We conclude that both GM-CSF and FLT3L act through PU.1 to activate the 5.3 Kb CD11c proximal promoter in DCs and to induce differentiation of monocyte-derived DCs. We also confirm that the CD11c proximal promoter is not sufficient to direct lineage specificity of CD11c expression, and that additional DNA elements are required

  14. Luminal progenitors restrict their lineage potential during mammary gland development.

    Science.gov (United States)

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  15. Reporter-Based Isolation of Developmental Myogenic Progenitors

    Directory of Open Access Journals (Sweden)

    Eyemen Kheir

    2018-04-01

    Full Text Available The formation and activity of mammalian tissues entail finely regulated processes, involving the concerted organization and interaction of multiple cell types. In recent years the prospective isolation of distinct progenitor and stem cell populations has become a powerful tool in the hands of developmental biologists and has rendered the investigation of their intrinsic properties possible. In this protocol, we describe how to purify progenitors with different lineage history and degree of differentiation from embryonic and fetal skeletal muscle by fluorescence-activated cell sorting (FACS. The approach takes advantage of a panel of murine strains expressing fluorescent reporter genes specifically in the myogenic progenitors. We provide a detailed description of the dissection procedures and of the enzymatic dissociation required to maximize the yield of mononucleated cells for subsequent FACS-based purification. The procedure takes ~6–7 h to complete and allows for the isolation and the subsequent molecular and phenotypic characterization of developmental myogenic progenitors.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte M.; Geisler, Carsten

    2016-01-01

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

  18. Imaging Findings of Localized Lymphoid Hyperplasia of the Pancreas: a Case Report

    International Nuclear Information System (INIS)

    Kim, Jin Woong; Heo, Suk Hee; Jeong, Yong Yeon; Kang, Heoung Keun; Shin, Sang Soo; Choi, Yoo Duk

    2011-01-01

    We report here on a case of localized lymphoid hyperplasia of the pancreas in a 70-year-old man which manifested as double lesions (uncinate process and tail) in the organ. The lesions were incidentally detected as hypoechoic lesions on ultrasonography and they appeared as delayed enhancing lesions on the contrast-enhanced dynamic CT and MRI. Total pancreatectomy was performed, because malignant tumor could not be excluded according to the preoperative imaging studies and the endoscopic ultrasound-guided biopsy failed. Pathology revealed localized lymphoid hyperplasia. The patient had an uneventful postoperative course. He has been alive for 18 months after surgery.

  19. Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut

    OpenAIRE

    Kim, Myung H.; Taparowsky, Elizabeth J.; Kim, Chang H.

    2015-01-01

    Distinct groups of innate lymphoid cells (ILCs) such as ILC1, ILC2 and ILC3 populate the intestine, but how these ILCs develop tissue tropism for this organ is unclear. We report that prior to migration to the intestine ILCs first undergo a `switch' in their expression of homing receptors from lymphoid to gut homing receptors. This process is regulated by mucosal dendritic cells and the gut-specific tissue factor retinoic acid (RA). This change in homing receptors is required for long-term po...

  20. Imaging Findings of Localized Lymphoid Hyperplasia of the Pancreas: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Woong; Heo, Suk Hee; Jeong, Yong Yeon; Kang, Heoung Keun [Chonnam National University Hwasun Hospital and Medical School, Hwasun (Korea, Republic of); Shin, Sang Soo; Choi, Yoo Duk [Chonnam National University Hospital and Medical School, Gwangju (KR)

    2011-08-15

    We report here on a case of localized lymphoid hyperplasia of the pancreas in a 70-year-old man which manifested as double lesions (uncinate process and tail) in the organ. The lesions were incidentally detected as hypoechoic lesions on ultrasonography and they appeared as delayed enhancing lesions on the contrast-enhanced dynamic CT and MRI. Total pancreatectomy was performed, because malignant tumor could not be excluded according to the preoperative imaging studies and the endoscopic ultrasound-guided biopsy failed. Pathology revealed localized lymphoid hyperplasia. The patient had an uneventful postoperative course. He has been alive for 18 months after surgery.

  1. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    Science.gov (United States)

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  2. Allograft tolerance in pigs after fractionated lymphoid irradiation. II. Kidney graft after conventional total lymphoid irradiation and bone marrow cell grafting

    International Nuclear Information System (INIS)

    Fradelizi, D.; Mahouy, G.; de Riberolles, C.; Lecompte, Y.; Alhomme, P.; Douard, M.C.; Chotin, G.; Martelli, H.; Daburon, F.; Vaiman, M.

    1981-01-01

    Experiments with pigs have been performed in order to establish bone marrow chimerism and kidney graft tolerance between SLA genotyped semi-incompatible animals. Recipients were conditioned by means of conventional fractionated total lymphoid irradiation (TLI) delivered by a vertical cobalt source. The principal lymphoid regions of the pig, including thymus and spleen, were submitted to irradiation. Two protocols were tested: A = 250 cGy four times a week x 13 times (TLI) (two animals) and B = 350 cGy three times a week x 8 times (TLI) (four animals). Bone marrow cells were injected 24 h after the last irradiation. One day later, bilateral nephrectomy and the graft of one kidney from the bone marrow cell donor were performed simultaneously. Results convinced us that application of the TLI protocol to humans is not yet practicable and that further experimental work is needed

  3. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    Science.gov (United States)

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  4. Biology and flow cytometry of proangiogenic hematopoietic progenitors cells.

    Science.gov (United States)

    Rose, Jonathan A; Erzurum, Serpil; Asosingh, Kewal

    2015-01-01

    During development, hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life, this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow (BM)-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative "endothelial progenitor cells" that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multidisciplinary expertise in flow cytometry, hematology, and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and BM. © 2014 International Society for Advancement of Cytometry.

  5. LINKING TYPE Ia SUPERNOVA PROGENITORS AND THEIR RESULTING EXPLOSIONS

    International Nuclear Information System (INIS)

    Foley, Ryan J.; Kirshner, Robert P.; Simon, Joshua D.; Burns, Christopher R.; Gal-Yam, Avishay; Hamuy, Mario; Morrell, Nidia I.; Phillips, Mark M.; Shields, Gregory A.; Sternberg, Assaf

    2012-01-01

    Comparing the ejecta velocities at maximum brightness and narrow circumstellar/interstellar Na D absorption line profiles of a sample of 23 Type Ia supernovae (SNe Ia), we determine that the properties of SN Ia progenitor systems and explosions are intimately connected. As demonstrated by Sternberg et al., half of all SNe Ia with detectable Na D absorption at the host-galaxy redshift in high-resolution spectroscopy have Na D line profiles with significant blueshifted absorption relative to the strongest absorption component, which indicates that a large fraction of SN Ia progenitor systems have strong outflows. In this study, we find that SNe Ia with blueshifted circumstellar/interstellar absorption systematically have higher ejecta velocities and redder colors at maximum brightness relative to the rest of the SN Ia population. This result is robust at a 98.9%-99.8% confidence level, providing the first link between the progenitor systems and properties of the explosion. This finding is further evidence that the outflow scenario is the correct interpretation of the blueshifted Na D absorption, adding additional confirmation that some SNe Ia are produced from a single-degenerate progenitor channel. An additional implication is that either SN Ia progenitor systems have highly asymmetric outflows that are also aligned with the SN explosion or SNe Ia come from a variety of progenitor systems where SNe Ia from systems with strong outflows tend to have more kinetic energy per unit mass than those from systems with weak or no outflows.

  6. Peripheral tissue homing receptor control of naïve, effector, and memory CD8 T cell localization in lymphoid and non-lymphoid tissues.

    Science.gov (United States)

    Brinkman, C Colin; Peske, J David; Engelhard, Victor Henry

    2013-01-01

    T cell activation induces homing receptors that bind ligands on peripheral tissue vasculature, programing movement to sites of infection and injury. There are three major types of CD8 effector T cells based on homing receptor expression, which arise in distinct lymphoid organs. Recent publications indicate that naïve, effector, and memory T cell migration is more complex than once thought; while many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and contain central memory precursors. LN re-entry can depend on CD62L or peripheral tissue homing receptors. Memory T cells in LN tend to express the same homing receptors as their forebears, but often are CD62Lneg. Homing receptors also control CD8 T cell tumor entry. Tumor vasculature has low levels of many peripheral tissue homing receptor ligands, but portions of it resemble high endothelial venules (HEV), enabling naïve T cell entry, activation, and subsequent effector activity. This vasculature is associated with positive prognoses in humans, suggesting it may sustain ongoing anti-tumor responses. These findings reveal new roles for homing receptors expressed by naïve, effector, and memory CD8 T cells in controlling entry into lymphoid and non-lymphoid tissues.

  7. Clues on Type Ia Supernovae Progenitors

    International Nuclear Information System (INIS)

    Piersanti, Luciano; Tornambe, Amedeo

    2005-01-01

    We show that in the framework of canonical stellar evolution it is hard, if not impossible, to determine the growth in mass of a CO White Dwarf, up to the Chandrasekhar limit by means of mass transfer from its companion in a binary system. This is the case either if matter is accreted from a normal companion with an H-rich envelope or if direct CO accretion occurs from a CO WD companion. At variance, we show that if the effects of rotation are taken into account in modeling the accretion process, a CO WD can increase its mass at the expenses of the degenerate CO companion up and beyond 1.4 M· , so that an explosive event of the type Ia class is naturally produced. This theoretical finding revives the Double Degenerate scenario for type Ia SNe progenitors. In such a case the internal spread in the observational properties of type Ia SNe may be interpreted as a consequence of different total masses; hence differences between SNe Ia in nearby elliptical galaxies and the majority of those in spirals should be expected and the current use of type Ia SNe as cosmological distance indicators should be justified

  8. TWEAK induces liver progenitor cell proliferation

    Science.gov (United States)

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

    2005-01-01

    Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  9. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  10. Role of liver progenitors in liver regeneration.

    Science.gov (United States)

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

    2015-02-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

  11. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  12. Enhanced genetic modification of adult growth factor mobilized peripheral blood hematopoietic stem and progenitor cells with rapamycin.

    Science.gov (United States)

    Li, Lijing; Torres-Coronado, Mónica; Gu, Angel; Rao, Anitha; Gardner, Agnes M; Epps, Elizabeth W; Gonzalez, Nancy; Tran, Chy-Anh; Wu, Xiwei; Wang, Jin-Hui; DiGiusto, David L

    2014-10-01

    Genetic modification of adult human hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors leads to long-term gene expression in the progeny of the HSPCs and has been used to successfully treat several monogenic diseases. In some cases, the gene-modified cells have a selective growth advantage over nonmodified cells and eventually are the dominant engrafted population. However, in disease indications for which the gene-modified cells do not have a selective advantage, optimizing transduction of HSPC is paramount to successful stem cell-based gene therapy. We demonstrate here that transduction of adult CD34+ HSPCs with lentiviral vectors in the presence of rapamycin, a widely used mTORC1 inhibitor, results in an approximately threefold increase in stable gene marking with minimal effects on HSPC growth and differentiation. Using this approach, we have demonstrated that we can enhance the frequency of gene-modified HSPCs that give rise to clonogenic progeny in vitro without excessive increases in the number of vector copies per cell or changes in integration pattern. The genetic marking of HSPCs and expression of transgenes is durable, and transplantation of gene-modified HSPCs into immunodeficient mice results in high levels of gene marking of the lymphoid and myeloid progeny in vivo. The prior safe clinical history of rapamycin in other applications supports the use of this compound to generate gene-modified autologous HSPCs for our HIV gene therapy clinical trials. ©AlphaMed Press.

  13. Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors

    NARCIS (Netherlands)

    Mega, Tiziana; Lupia, Michela; Amodio, Nicola; Horton, Sarah J.; Mesuraca, Maria; Pelaggi, Daniela; Agosti, Valter; Grieco, Michele; Chiarella, Emanuela; Spina, Raffaella; Moore, Malcolm A. S.; Schuringa, Jan Jacob; Bond, Heather M.; Morrone, Giovanni

    2011-01-01

    Zinc finger protein 521 (EHZF/ZNF521) is a multi-functional transcription co-factor containing 30 zinc fingers and an N-terminal motif that binds to the nucleosome remodelling and histone deacetylase (NuRD) complex. ZNF521 is believed to be a relevant player in the regulation of the homeostasis of

  14. Regular character of chromatin degradation in lymphoid tissues after treatment with biological alkylating agents in vivo

    International Nuclear Information System (INIS)

    Matyasova, J.; Skalka, M.; Cejkova, M.

    1979-01-01

    The chromatin changes are reevaluated occurring in lymphoid tissues of mice treated with alkylating agents of the nitrogen-mustard type in relation to recent evidence on the nucleosomal organization of chromatin and to our new data on the regular character of chromatin degradation in lymphoid tissues of irradiated mice. DNA was isolated from nuclei at various intervals (1 to 18 h) after treatment of mice and subjected to gel electrophoresis in polyacrylamide gels. Thymus chromatin from treated mice has been shown to degrade in a regular fashion and to yield discrete DNA fragments, resembling those that originate in lymphoid tissues of irradiated mice or in thymus nuclei digested with micrococcal nuclease in vitro. With increasing interval after treatment higher amounts of smaller DNA fragments appear. Chromatin in spleen cells responds to treatment in a similar way, whilst no degradation in vivo takes place in liver chromatin. Chromatin of LS/BL lymphosarcoma cells in mice treated with alkylating agents or with irradiation suffers from a similar regular degradation. The results stress the significance of the action of liberated or activated endogenous nuclease(s) in the development of chromatin damage in lymphoid cells after treatment with alkylating agents. (author)

  15. Case of CML lymphoid blast crisis presenting as bilateral breast masses.

    Science.gov (United States)

    Hossain, Aneesha; Gupta, Kanika; Mener, Andrew; Tabbara, Imad

    2016-08-10

    A woman aged 42 years with a 1-month history of rapidly expanding bilateral breast masses presented with severe leucocytosis, anaemia, blurry vision, headaches and shortness of breath. Evaluation revealed chronic myeloid leukaemia in lymphoid blast crisis with extramedullary leukaemia involving her breasts. 2016 BMJ Publishing Group Ltd.

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

    International Nuclear Information System (INIS)

    Mehta, J.; Singhal, S.; Huilgol, N.; Merchant, R.; Mehta, B.C.

    1992-01-01

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

  17. The 2016 revision of the World Health Organization classification of lymphoid neoplasms | Center for Cancer Research

    Science.gov (United States)

    A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities.

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

    NARCIS (Netherlands)

    J.G. Noordzij

    2002-01-01

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

  19. Microscopic aspects of lymphoid organs in the guinea pig (Cavia porcellus

    Directory of Open Access Journals (Sweden)

    Fernanda Menezes de Oliveira e Silva

    2013-10-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2013v26n4p233 Microscopy of lymphoid organs was studied in the guinea pig at different developmental stages – fetus, pup, and adult. Liver is a lobed organ, coated with a mesothelium, and it consists of sinusoids and cell plates in its parenchyma, named hepatocytes. Thymus is covered by a thin capsule of connective tissue which is protruded as septa into the entire organ. The parenchyma of each lobule is not clearly separated into a cortex and medulla. Hassall’s corpuscles are abundant. Lymph nodes are arranged into cortex and medulla. The cortex has germinal centers or lymphoid nodules, surrounded by diffuse lymphoid tissue. Spleen is divided into red and white pulp. Trabeculae of connective tissue are protruded into the spleen from the capsule; however, they are sparsely found around the red and white pulps. Germinal centers were found in the white pulp, where small and large lymphocytes and lymphoblasts can be found. Since the guinea pig is regarded as an important model for morphological studies due to its closeness to human beings, this article raises relevant information on the structural components of the lymphoid system in these animals, providing a new source of data to other knowledge fields.

  20. Microscopic aspects of lymphoid organs in the guinea pig (Cavia porcellus

    Directory of Open Access Journals (Sweden)

    Fernanda Menezes de Oliveira e Silva

    2013-11-01

    Full Text Available Microscopy of lymphoid organs was studied in the guinea pig at different developmental stages – fetus, pup, and adult. Liver is a lobed organ, coated with a mesothelium, and it consists of sinusoids and cell plates in its parenchyma, named hepatocytes. Thymus is covered by a thin capsule of connective tissue which is protruded as septa into the entire organ. The parenchyma of each lobule is not clearly separated into a cortex and medulla. Hassall’s corpuscles are abundant. Lymph nodes are arranged into cortex and medulla. The cortex has germinal centers or lymphoid nodules, surrounded by diffuse lymphoid tissue. Spleen is divided into red and white pulp. Trabeculae of connective tissue are protruded into the spleen from the capsule; however, they are sparsely found around the red and white pulps. Germinal centers were found in the white pulp, where small and large lymphocytes and lymphoblasts can be found. Since the guinea pig is regarded as an important model for morphological studies due to its closeness to human beings, this article raises relevant information on the structural components of the lymphoid system in these animals, providing a new source of data to other knowledge fields.

  1. Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Malignancies.

    Science.gov (United States)

    Varughese, Tilly; Taur, Ying; Cohen, Nina; Palomba, M Lia; Seo, Susan K; Hohl, Tobias M; Redelman-Sidi, Gil

    2018-03-02

    Ibrutinib is a Bruton's tyrosine kinase inhibitor that is used for the treatment of lymphoid malignancies, including chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia and mantle cell lymphoma (MCL). Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. We reviewed the electronic medical records of patients with lymphoid malignancies at Memorial Sloan Kettering Cancer Center who received ibrutinib during a five-year period from January 1, 2012 to December 31, 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by univariate and multivariate analyses. 378 patients with lymphoid malignancies who received ibrutinib were analyzed. The most common underlying malignancies were CLL and MCL. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Of these, 23 (53.5%) developed invasive bacterial infections, and 16 (37.2%) developed invasive fungal infections (IFI). The majority of those who developed IFI on ibrutinib therapy (62.5%) lacked classical clinical risk factors for fungal infection (i.e., neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in six of the 43 patients (14%). Patients with lymphoid malignancies receiving ibrutinib treatment are at risk for serious infections, including IFI.

  2. Disseminated Cryptococcosis With Brain Involvement in Patients With Chronic Lymphoid Malignancies on Ibrutinib.

    Science.gov (United States)

    Messina, Julia A; Maziarz, Eileen K; Spec, Andrej; Kontoyiannis, Dimitrios P; Perfect, John R

    2017-01-01

    We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

  3. Disseminated Cryptococcosis With Brain Involvement in Patients With Chronic Lymphoid Malignancies on Ibrutinib

    OpenAIRE

    Messina, Julia A.; Maziarz, Eileen K.; Spec, Andrej; Kontoyiannis, Dimitrios P.; Perfect, John R.

    2017-01-01

    Abstract We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

  4. Treatment of Mucosa-associated Lymphoid Tissue Lymphoma in Sjogren's Syndrome : A Retrospective Clinical Study

    NARCIS (Netherlands)

    Pollard, Rodney P. E.; Pijpe, Justin; Bootsma, Hendrika; Spijkervet, Fred K. L.; Kluin, Philip M.; Roodenburg, Jan L. N.; Kallenberg, Cees G. M.; Vissink, Arjan; van Imhoff, Gustaaf W.

    2011-01-01

    Objective. To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sjogren's syndrome (SS). Methods. All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical

  5. S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense

    Science.gov (United States)

    Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...

  6. Establishment and function of tissue-resident innate lymphoid cells in the skin

    Directory of Open Access Journals (Sweden)

    Jie Yang

    2017-03-01

    Full Text Available ABSTRACT Innate lymphoid cells (ILCs are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

  7. Th1- and Th2-like subsets of innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, Jochem; Mjösberg, Jenny; Spits, Hergen

    2013-01-01

    Innate lymphoid cells (ILCs) constitute a family of effectors in innate immunity and regulators of tissue remodeling that have a cytokine and transcription factor expression pattern that parallels that of the T-helper (Th) cell family. Here, we discuss how ILCs can be categorized and summarize the

  8. Establishment and function of tissue-resident innate lymphoid cells in the skin.

    Science.gov (United States)

    Yang, Jie; Zhao, Luming; Xu, Ming; Xiong, Na

    2017-07-01

    Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

  9. Innate Lymphoid Cells (ILCs): Cytokine Hubs Regulating Immunity and Tissue Homeostasis

    NARCIS (Netherlands)

    Nagasawa, Maho; Spits, Hergen; Ros, Xavier Romero

    2017-01-01

    Innate lymphoid cells (ILCs) have emerged as an expanding family of effector cells particularly enriched in the mucosal barriers. ILCs are promptly activated by stress signals and multiple epithelial- and myeloid-cell-derived cytokines. In response, ILCs rapidly secrete effector cytokines, which

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

    NARCIS (Netherlands)

    Spits, H.

    2011-01-01

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

  11. Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis

    International Nuclear Information System (INIS)

    Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

    1978-01-01

    The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log 10 PD 50 values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplanted Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain

  12. Ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiotherapy

    International Nuclear Information System (INIS)

    Ejima, Yasuo; Sasaki, Ryohei; Okamoto, Yoshiaki; Maruta, Tsutomu; Azumi, Atsushi; Hayashi, Yoshitake; Demizu, Yusuke; Ota, Yosuke; Soejima, Toshinori; Sugimura, Kazuro

    2006-01-01

    Forty-two patients with stage IE ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma were retrospectively analyzed. Five-year local control and progression-free survival rates were 100 and 77%, respectively. The most common relapsed site was the contralateral orbit. Thirty Gy of local irradiation seemed to be quite effective and safe

  13. Tracheal involvement of bronchus-associated lymphoid tissue lymphoma: a case report

    International Nuclear Information System (INIS)

    Sohn, Kyung Sik; Jeon, Kyung Neough; Kang, Duk Sik

    2002-01-01

    Primary malignant tumors of the trachea are rare, the most prevalent histologies beeing squamous cell and adenoid cystic carcinoma. A review of the literature revealed only ten cases of primary tracheal or bronchial non-Hodgkin's lymphoma. We describe a case in which tracheal involvement of bronchus-associated lymphoid tissue lymphoma, a subtype of non-Hodgkin's lymphoma, occurred

  14. Most B cells in non-lymphoid tissues are naïve.

    Science.gov (United States)

    Inman, Charlotte F; Murray, Tamsin Zangerle; Bailey, Mick; Cose, Stephen

    2012-02-01

    The current view of lymphocyte migration states that naïve lymphocytes re-circulate between the blood and the lymph via the lymph nodes, but are not able to access non-lymphoid tissues. We examined B lymphocytes in peripheral tissues and found that the majority were phenotypically similar to naïve B cells in lymphoid tissues and were located within the parenchyma, not associated with blood vessels. The mutation rate within the Vh region of these cells was substantially less than the rate attributed to somatic hypermutation and was identical to that observed in naïve B cells isolated from the lymph nodes, showing the presence of naïve B cells in the non-lymphoid organs. Further, using FTY720-treated mice, we showed that naïve B cells migrate through the peripheral tissues and, using pertussis toxin, that the entry of B cells was not controlled by chemokine-mediated signalling events. Overall, these results show that naïve B lymphocytes constitute the majority of the total B-cell population in non-lymphoid tissues and suggest that these cells may re-circulate through the periphery as part of their normal migration pathway. This has implications for the current view of the role of naïve B cells in priming and tolerance.

  15. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Kim, Bong Jae; Seo, Jung Wook; Lee, Byung Hoon

    2009-01-01

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

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

    NARCIS (Netherlands)

    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

    2014-01-01

    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

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-15

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

  20. Derangements of lacrimal drainage-associated lymphoid tissue (LDALT) in human chronic dacryocystitis.

    Science.gov (United States)

    Ali, Mohammad Javed; Mulay, Kaustubh; Pujari, Aditi; Naik, Milind N

    2013-12-01

    To study the changes in the lacrimal drainage-associated lymphoid tissue of the lacrimal sac in human chronic dacryocystitis and its possible implications in understanding the immune defense mechanisms and etiopathogenesis of primary acquired nasolacrimal duct obstruction. Retrospective interventional study involving 200 lacrimal sacs of 164 consecutive patients seen between July 2009 and July 2012. Data collected include demographics, clinical presentation, laterality, age at presentation, duration of symptoms, diagnostic irrigation, indications for a dacyrocystectomy, pattern and severity of lymphoid infiltrate, types of lymphoid follicles and their locations, plasma cells, and other cellular infiltrates. The associated epithelial, stromal, and luminal changes with an emphasis on acini, mucosal glands, blood vessels, lymphatics, and goblet cells were also noted. Immunohistochemistry using CD3, CD20, CD138, and immunoglobulin A were used to substantiate the lymphoid tissues of the lacrimal sac. A total of 200 lacrimal sacs were obtained from dacryocystectomy of 164 patients. The patients included 60.5% (99/164) females and 39.6% (65/164) males, with a mean age of 58.4 years at presentation. Laterality showed a predominance of left lacrimal sacs (55%, 110/200) as compared to the right lacrimal sacs (45%, 90/200). Symptoms of epiphora and discharge of more than 6 months duration were considered to be chronic. Lymphoid infiltrate pattern was diffuse in majority of the sacs (81%, 162/200), with subepithelial and intraepithelial together being the commonest location (46.5%, 93/200). Distinct lymphoid follicles were seen in 28% (56/200). Most of the sacs showed mild plasma cell infiltration (66.5%, 133/200). IgA-rich secretions were noted in the lumen and the lining epithelium in 34.5% (69/200). Other common changes noted include increase in the goblet cells (82%, 164/200), dilated lymphatics (94%, 188/200), proliferating blood vessels (99%, 198/200), thickened

  1. Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system.

    Science.gov (United States)

    Knop, E; Knop, N

    2001-03-01

    Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal surfaces. In a previous study of the human conjunctiva, evidence was also found for the presence of MALT in the lacrimal sac. The present study, therefore, aims to investigate its morphology and topographical distribution in the human lacrimal drainage system. Lacrimal drainage systems (n = 51) obtained from human cadavers were investigated by clearing flat wholemounts or by serial sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were further analyzed by histology, immunohistochemistry, and electron microscopy. All specimens showed the presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria, together with intraepithelial lymphocytes and occasional high endothelial venules (HEV). It formed a narrow layer along the canaliculi that became thicker in the cavernous parts. The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centers. T cells were positive for CD8 and the human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA and the overlying epithelium expressed its transporter molecule secretory component (SC). Basal mucous glands were present in the lacrimal canaliculi and in the other parts accompanied by alveolar and acinar glands, all producing IgA-rich secretions. Primary and secondary lymphoid follicles possessing HEV were present in about half of the specimens. The term lacrimal drainage-associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid tissue that is regularly present and belongs to the common mucosal immune system and to the secretory immune system. It is suggested that it may form a functional unit together with the lacrimal gland and conjunctiva, connected by tear flow, lymphocyte recirculation, and probably the neural reflex arc, and play a major role in preserving ocular surface integrity.

  2. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    Science.gov (United States)

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.

  3. THE TYPE IIb SUPERNOVA 2011dh FROM A SUPERGIANT PROGENITOR

    International Nuclear Information System (INIS)

    Bersten, Melina C.; Nomoto, Ken'ichi; Folatelli, Gastón; Maeda, Keiichi; Benvenuto, Omar G.; Ergon, Mattias; Sollerman, Jesper; Benetti, Stefano; Ochner, Paolo; Tomasella, Lina; Botticella, Maria Teresa; Fraser, Morgan; Kotak, Rubina

    2012-01-01

    A set of hydrodynamical models based on stellar evolutionary progenitors is used to study the nature of SN 2011dh. Our modeling suggests that a large progenitor star—with R ∼ 200 R ☉ —is needed to reproduce the early light curve (LC) of SN 2011dh. This is consistent with the suggestion that the yellow super-giant star detected at the location of the supernova (SN) in deep pre-explosion images is the progenitor star. From the main peak of the bolometric LC and expansion velocities, we constrain the mass of the ejecta to be ≈2 M ☉ , the explosion energy to be E = (6-10) × 10 50 erg, and the 56 Ni mass to be approximately 0.06 M ☉ . The progenitor star was composed of a helium core of 3-4 M ☉ and a thin hydrogen-rich envelope of ≈0.1M ☉ with a main-sequence mass estimated to be in the range of 12-15 M ☉ . Our models rule out progenitors with helium-core masses larger than 8 M ☉ , which correspond to M ZAMS ∼> 25M ☉ . This suggests that a single star evolutionary scenario for SN 2011dh is unlikely.

  4. NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis

    Science.gov (United States)

    Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael

    2014-01-01

    Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739

  5. Strategies to reverse endothelial progenitor cell dysfunction in diabetes.

    Science.gov (United States)

    Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo

    2012-01-01

    Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  6. Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Alessandra Petrelli

    2012-01-01

    Full Text Available Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial, their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs. Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.

  7. Development and molecular composition of the hepatic progenitor cell niche.

    Science.gov (United States)

    Vestentoft, Peter Siig

    2013-05-01

    End-stage liver diseases represent major health problems that are currently treated by liver transplantation. However, given the world-wide shortage of donor livers novel strategies are needed for therapeutic treatment. Adult stem cells have the ability to self-renew and differentiate into the more specialized cell types of a given organ and are found in tissues throughout the body. These cells, whose progeny are termed progenitor cells in human liver and oval cells in rodents, have the potential to treat patients through the generation of hepatic parenchymal cells, even from the patient's own tissue. Little is known regarding the nature of the hepatic progenitor cells. Though they are suggested to reside in the most distal part of the biliary tree, the canal of Hering, the lack of unique surface markers for these cells has hindered their isolation and characterization. Upon activation, they proliferate and form ductular structures, termed "ductular reactions", which radiate into the hepatic parenchyma. The ductular reactions contain activated progenitor cells that not only acquire a phenotype resembling that observed in developing liver but also display markers of differentiation shared with the cholangiocytic or hepatocytic lineages, the two parenchymal hepatic cell types. Interactions between the putative progenitor cells, the surrounding support cells and the extracellular matrix scaffold, all constituting the progenitor cell niche, are likely to be important for regulating progenitor cell activity and differentiation. Therefore, identifying novel progenitor cell markers and deciphering their microenvironment could facilitate clinical use. The aims of the present PhD thesis were to expand knowledge of the hepatic progenitor cell niche and characterize it both during development and in disease. Several animal models of hepatic injury are known to induce activation of the progenitor cells. In order to identify possible progenitor cell markers and niche components

  8. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  9. Establishment of bipotent progenitor cell clone from rat skeletal muscle.

    Science.gov (United States)

    Murakami, Yousuke; Yada, Erica; Nakano, Shin-ichi; Miyagoe-Suzuki, Yuko; Hosoyama, Tohru; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  10. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael [Univ. of California, Berkeley, CA (United States)

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of rV = 4.26$+1.39 +0.10\\atop{-1.93 -0.10}$h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  11. Rates and progenitors of type Ia supernovae

    International Nuclear Information System (INIS)

    Wood-Vasey, William Michael

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ∼ 0.01-0.1 of r V = 4.26 -1.93 -0.10 +1.39 +0.10 h 3 x 10 -4 SNe Ia/yr/Mpc 3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae

  12. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

    Full Text Available Qing Wang,1,* Qi Wu,2,* Jing Feng,3,4 Xin Sun5 1The Second Respiratory Department of the First People's Hospital of Kunming, Yunnan, People's Republic of China; 2Tianjin Haihe Hospital, Tianjin, People's Republic of China; 3Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 4Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA; 5Respiratory Department of Tianjin Haihe Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Background: Obstructive sleep apnea (OSA occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow–derived endothelial progenitor cells (EPCs within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. Methods: We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Conclusion: Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has

  13. File list: ALL.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.50.AllAg.Multipotent_otic_progenitor mm9 All antigens Others Multipotent otic progeni...ncedbc.jp/kyushu-u/mm9/assembled/ALL.Oth.50.AllAg.Multipotent_otic_progenitor.bed ...

  14. File list: ALL.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Induced_neural_progenitors mm9 All antigens Neural Induced neural progeni....biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  15. File list: ALL.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.10.AllAg.Induced_neural_progenitors mm9 All antigens Neural Induced neural progeni....biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.10.AllAg.Induced_neural_progenitors.bed ...

  16. Regulation of Mammary Progenitor Cells by p53 and Parity

    Science.gov (United States)

    2011-01-01

    quantitative PCR system (Stratagene). To knockdown Notch1 in TM40A cells, siRNA (s70698 and s70700) were purchased from Ambion. s70698 siRNA sense sequence: 5...hours after transfect ion and real-tim e quantitative P CR was used to confirm the knockdown efficiency. Results Label and chase progenitor cells...cells contained 0.8% o f DsRed positiv e (DsR +) progenitor cells (Fig. 1B). The mammosphere-forming capacity of DsR+ cells is 3.8-fold greater

  17. Effect of alkaline and acidic fractions of industrial effluents on some lymphoid cells of the fish Rasbora daniconius

    Energy Technology Data Exchange (ETDEWEB)

    Elizabeth, T K; Balasubramanian, N K; John, P A

    1981-01-01

    The percentage frequency of the different types of lymphoid cell found in the head-kidney of Rasbora daniconius exposed for 24 h to lc/sub 50/ levels of the ammonia (alkali), phosphoric and sulphuric acid fractions of the effluent from a fertiliser factory was determined by the imprint method. 'T' tests showed that both the alkaline and the acidic fractions could significantly affect the composition of the lymphoid cell population. Different types of lymphoid cell reacted differently to the different fractions; some cell types increased in number while others decreased. Some cell types were not affected. This indicated some sort of specificity in the action of the fractions on the lymphoid cells.

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

    International Nuclear Information System (INIS)

    Lee, Sang Kwon; Kwon, Sun Young; Kim, Young Hwan; Choi, Jin Soo; Sohn, Chul Ho; Lee, Hee Jung; Woo, Seong Ku; Suh, Soo Ji

    2006-01-01

    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

  19. In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

    Science.gov (United States)

    Lew, Y Y; Michalak, T I

    2001-02-01

    Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

  20. IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Shaw, Joanne L; Fakhri, Samer; Citardi, Martin J; Porter, Paul C; Corry, David B; Kheradmand, Farrah; Liu, Yong-Jun; Luong, Amber

    2013-08-15

    Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

  1. Central Role of Core Binding Factor β2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse.

    Science.gov (United States)

    Nagatake, Takahiro; Fukuyama, Satoshi; Sato, Shintaro; Okura, Hideaki; Tachibana, Masashi; Taniuchi, Ichiro; Ito, Kosei; Shimojou, Michiko; Matsumoto, Naomi; Suzuki, Hidehiko; Kunisawa, Jun; Kiyono, Hiroshi

    2015-01-01

    Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer's patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT.

  2. Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function.

    Science.gov (United States)

    Kielczewski, Jennifer L; Horai, Reiko; Jittayasothorn, Yingyos; Chan, Chi-Chao; Caspi, Rachel R

    2016-02-01

    During chronic inflammation, tertiary lymphoid tissue (TLT) can form within an inflamed organ, including the CNS. However, little is known about TLT formation in the neuroretina. In a novel spontaneous autoimmune mouse model of uveitis (R161H), we identified well-organized lymphoid aggregates in the retina and examined them for TLT characteristics. Presence of immune cells, tissue-specific markers, and gene expression patterns typically associated with germinal centers and T follicular helper cells were examined using immunohistochemistry and gene analysis of laser capture microdissected retina. Our data revealed the retinal lymphoid structures contained CD4(+) T cells and B cells in well-defined zonal areas that expressed classic germinal center markers, peanut lectin (agglutinin) and GL-7. Gene expression analysis showed upregulation of T follicular helper cell markers, most notably CXCR5 and its ligand CXCL13, and immunohistochemical analysis confirmed CXCR5 expression, typically associated with CD4(+) T follicular helper cells. Highly organized stromal cell networks, a hallmark of organized lymphoid tissue, were also present. Positive staining for phospho-Zap70 in retina-specific T cells indicated CD4(+) T cells were being activated within these lymphoid structures. CD138(+)/B220(+) plasma cells were detected, suggesting the retinal lymphoid aggregates give rise to functional germinal centers, which produce Abs. Interestingly, eyes with lymphoid aggregates exhibited lower inflammatory scores by fundus examination and a slower initial rate of loss of visual function by electroretinography, compared with eyes without these structures. Our findings suggest that the lymphoid aggregates in the retina of R161H mice represent organized TLT, which impact the course of chronic uveitis.

  3. Safe and successful birth following pelvic radiotherapy for rectal mucosa-associated lymphoid tissue lymphoma: a case report.

    Science.gov (United States)

    Hatayama, Yoshiomi; Aoki, Masahiko; Kawaguchi, Hideo; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Tanaka, Mitsuki; Fujioka, Ichitaro; Ono, Shuichi; Takai, Yoshihiro

    2017-02-01

    Mucosa-associated lymphoid tissue lymphomas can occur in various parts of the body, and half of mucosa-associated lymphoid tissue lymphomas occur in the gastrointestinal tract. Gastric mucosa-associated lymphoid tissue lymphoma is the most common lymphoma of the gastrointestinal tract and primary rectal mucosa-associated lymphoid tissue lymphoma is very rare. Because of the high radiosensitivity of mucosa-associated lymphoid tissue lymphomas, this condition can be controlled with radiotherapy of approximately 30 Gy alone. However, ovarian dysfunction as an adverse event of radiotherapy for pelvic lesions can become a problem in girls and women. We report a case of a 28-year-old woman with rectal mucosa-associated lymphoid tissue lymphoma who safely gave birth to a baby following 30.6 Gy radiotherapy to her whole rectum. A 28-year-old Japanese woman became aware of bloody stools and was diagnosed as having Lugano I rectal mucosa-associated lymphoid tissue lymphoma. She was referred to our institute and initiated on radiotherapy. However, she expressed a desire to bear children. We used horizontally opposed pair fields for radiotherapy to minimize the irradiation to her endometrium and ovary. A total dose of 30.6 Gy was given in 17 fractions of 1.8 Gy by 10-Megavolt X-ray linear accelerator. As a result, one-third of her uterus and half of her ovary were outside the irradiation field. After approximately 1 year of treatment, positive pregnancy was confirmed and finally she safely gave birth to a baby girl without congenital abnormalities. This report provides hope for girls and women who have undergone irradiation for pelvic mucosa-associated lymphoid tissue lymphomas and who desire to bear children.

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  5. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    Science.gov (United States)

    Foster, B. R.

    1975-01-01

    A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.

  6. Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

    Science.gov (United States)

    Pishdadian, Abbas; Varasteh, Abdol-Reza; Sankian, Mojtaba

    2012-01-01

    Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma. PMID:23209480

  7. Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update).

    Science.gov (United States)

    Yazdani, Reza; Sharifi, Mehri; Shirvan, Aylar Saba; Azizi, Gholamreza; Ganjalikhani-Hakemi, Mazdak

    2015-01-01

    Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and regulators of innate immunity. Although these cells are morphologically similar to B cells and T cells, however they do not express antigen receptors. ILCs seems to have emerging roles in innate immune responses against infectious or non-infectious microorganisms, protection of the epithelial barrier, lymphoid organogenesis and inflammation, tissue remodeling and regulating homeostasis of tissue stromal cells. In addition, it has recently been reported that ILCs have a crucial role in several disorders such as allergy and autoimmunity. Based on their phenotype and functions, ILCs are classified into three major groups called ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse ILC phenotypes, subclasses, functions in immune responses as well as in immune mediated disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-09-01

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

  9. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    Science.gov (United States)

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received...... an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97......%, respectively; Pblood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28...

  11. Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

    Science.gov (United States)

    Hwang, Ji Young; Randall, Troy D; Silva-Sanchez, Aaron

    2016-01-01

    Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

  12. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    Science.gov (United States)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  13. Protruding and non-protruding colon carcinomas originating in gut-associated lymphoid tissue.

    Science.gov (United States)

    Rubio, Carlos A; Lindh, Claes; Björk, Jan; Törnblom, Hans; Befrits, Ragnar

    2010-07-01

    Colon carcinomas arising in gut-associated lymphoid tissue (GALTC) are termed dome carcinomas (DC) because of their protruding phenotype. Only 8 GALTC cases have been reported in the literature. A female patient, aged 53, having a familial pedigree of colon cancer, uterine cervix cancer and brain tumour developed a signet-ring carcinoma in the cecum and 10 years later endometrial cancer. While asymptomatic, a plaque-like protrusion in the colon was detected at surveillance colonoscopy. Histology demonstrated a protruding GALTC. The surgical specimen showed four additional carcinomas: 2 GALTC (non-protruding) and 2 carcinomas in lymphoid-free colonic mucosa (LFCMC). Since adenomas could not be demonstrated neither previously nor in the colectomy specimen, it is suggested that the GALTCs in this patient may have followed the GALT-carcinoma pathway.

  14. Generation of Immunoglobulin diversity in human gut-associated lymphoid tissue.

    Science.gov (United States)

    Spencer, Jo; Barone, Francesca; Dunn-Walters, Deborah

    2009-06-01

    The organised gut associated lymphoid tissue (GALT) exists adjacent to an extensive and diverse luminal flora. The follicle associated epithelium and associated dendritic cells and lymphocytes form a tightly fortified gateway between the flora and the host that permits connectivity between them and chronic activation of the lymphoid compartment. As a consequence, plasma cell precursors are generated continuously, and in abundance, in GALT by clonal proliferation. Clonal proliferation alone on this scale would reduce the spectrum of B cell specificity. To compensate, GALT also houses molecular machinery that diversifies the receptor repertoire by somatic hypermutation, class switch recombination and receptor revision. These three processes of enhancing the diversity of mature B cells ensure that although clonally related plasma cells may secrete immunoglobulin side by side in the mucosa they rarely have identical antigen binding sites.

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

    Science.gov (United States)

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    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.

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  17. File list: Oth.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  18. File list: Pol.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  20. File list: Oth.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  1. File list: His.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  6. File list: Oth.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  7. File list: DNS.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  8. File list: His.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

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  9. File list: Unc.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  12. File list: Unc.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  13. File list: Pol.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

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  14. File list: His.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

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  16. File list: Pol.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  1. File list: Unc.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  8. File list: DNS.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

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  9. Abnormal Wnt signaling and stem cell activation in reactive lymphoid tissue and low-grade marginal zone lymphoma.

    Science.gov (United States)

    Zhang, Da; O'neil, Maura F; Cunningham, Mark T; Fan, Fang; Olyaee, Mojtaba; Li, Linheng

    2010-05-01

    The variable natural history of mucosa-associated lymphoid tissue (MALT) lymphoma poses a challenge in predicting clinical outcome. Since Wnt signaling, as indicated by nuclear localization of beta-catenin, is believed to be key in stem cell activation and stem cell self-renewal, we explored the possibility that it might have a predictive value in marginal zone lymphoma. We chose to analyze pbeta-catenin-S552 because its nuclear localization by immunohistochemistry appears to coincide with Wnt signaling-initiated tumorigenesis in intestinal and hematopoietic tissues. Wnt signaling and activation was studied in 22 tissue samples of extranodal marginal zone lymphoma, atypical lymphoid hyperplasia, reactive lymphoid hyperplasia, and normal lymphoid tissue to determine whether Wnt signaling could help distinguish MALT lymphoma from benign lesions. Compared to normal or reactive lymphoid tissue, we found increased nuclear expression of localized pbeta-catenin-S552 in atypical lymphoid hyperplasia and extranodal marginal zone lymphoma. We show that the anti-pbeta-catenin-S552 antibody may be useful in diagnosing and monitoring the progression of or response to therapy of MALT lymphoma.

  10. Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells.

    Science.gov (United States)

    Pizzolla, Angela; Wang, Zhongfang; Groom, Joanna R; Kedzierska, Katherine; Brooks, Andrew G; Reading, Patrick C; Wakim, Linda M

    2017-05-16

    The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8 + T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine. Whereas NALTs served as the induction site for the recall expansion of memory CD8 + T cells following influenza virus infection or vaccination, they failed to support activation of naïve CD8 + T cells. Strikingly, NALTs, unlike other lymphoid tissues, were not routinely surveyed during the steady state by circulating T cells. The selective recruitment of memory T cells into these lymphoid structures occurred in response to infection-induced elevation of the chemokine CXCL10, which attracted CXCR3 + memory CD8 + T cells. These results have significant implications for intranasal vaccines, which deliver antigen to mucosal-associated lymphoid tissue and aim to elicit protective CTL-mediated immunity.

  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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Morphological Studies on the Postnatal Development of the Gut-associated Lymphoid Tissues of the Rabbit Cecum

    Directory of Open Access Journals (Sweden)

    Abdelmohaimen M. Saleh

    2012-10-01

    Full Text Available The macroscopic, morphometric, light and scanning electron microscopic structure of gut-associated lymphoid tissue (GALT of cecum were studied in the rabbits aged from birth to 16 weeks. The GALT were formed of lymph follicles covered by low columnar epithelium containing intraepithelial lymphocytes and leukocytes. They were concentrated at the ileocecal entrance (ileocecal patch and in the blind end of the cecum vermiform appendix. In the ileocecal patch, GALT were in direct contact with the lumen, while those of the appendix were covered by the interval intestinal villi in young rabbits and mucosal folds in the adult rabbits. The lymphoid follicles of the ileocecal patch were composed of dome region and germinal center and were separated by narrow inter-follicular areas. Whereas, the lymphoid follicles of the appendix were composed dome region and germinal center in the newly born rabbits and up to the 2nd week of age, the follicles became composed of four different sites: dome region, germinal center, coronal area, and a wide interfollicular area between neighboring follicles. Morphometrically; the dimensions of the lymphoid follicles of the cecal GALT increased in size with the advancement of the age. By SEM the lymphoid structures covered with special epithelium consisted of two types of cell absorptive enterocytes and M cells. The M cells in the cecal patch were microvilliated and present on the tips and sides of the dome lymphoid regions while in the appendix were non-microvilliated and present only on the sides of the dome regions.

  13. Classical swine fever virus induces pyroptosis in the peripheral lymphoid organs of infected pigs.

    Science.gov (United States)

    Yuan, Jin; Zhu, Mengjiao; Deng, Shaofeng; Fan, Shuangqi; Xu, Hailuan; Liao, Jiedan; Li, Peng; Zheng, Jingfang; Zhao, Mingqiu; Chen, Jinding

    2018-05-02

    Classical swine fever virus (CSFV) causes a highly lethal disease in pigs, which is characterized by immunosuppression. Leukopenia is known to be a possible mechanism of immunosuppression during CSFV infection. As a new and specialized form of cell death, pyroptosis is the key response of the innate immune system to pathogens, and is widely involved in the occurrence and development of infectious diseases. However, the relationship between CSFV and pyroptosis has not been explored. In this study, we investigated the occurrence of pyroptosis in pigs following CSFV infection. According to qRT-PCR assay results, the prevalence of this virus in peripheral lymphoid organs (tonsils, lymph nodes, and spleen) was much higher than that in other organs. Severe bleeding, necrosis, and a significant reduction in lymphocytes were found in the peripheral lymphoid organs of CSFV-infected pigs based on histological examination. In-depth studies showed that an increased ratio of deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells were present in the peripheral lymphoid organs of the CSFV-infected group according to immunohistochemistry. Meanwhile, the p10 subunit and activity of caspase-1, which is a regulator of pyroptosis, the N-terminal domain of gasdermin D, which is an executor of pyroptosis, and the cleavage and secretion of IL-1b, which is a product of pyroptosis were increased in the peripheral lymphoid organs of the CSFV-infected group. Together, these results demonstrated that pyroptosis is involved in CSFV-induced cell death in vivo, which provides a new understanding of the mechanism associated with lymphocyte depletion and immunosuppression in pigs infected with this virus. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Clinical Impact of the Immunome in Lymphoid Malignancies: The Role of Myeloid-Derived Suppressor Cells

    Science.gov (United States)

    Vetro, Calogero; Romano, Alessandra; Ancora, Flavia; Coppolino, Francesco; Brundo, Maria V.; Raccuia, Salvatore A.; Puglisi, Fabrizio; Tibullo, Daniele; La Cava, Piera; Giallongo, Cesarina; Parrinello, Nunziatina L.

    2015-01-01

    The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells (MDSCs) have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of MDSCs in the settings of lymphoid malignancies. PMID:26052505

  15. Spectrum of lymphoid hyperplasia: Colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease

    International Nuclear Information System (INIS)

    Ell, S.R.; Frank, P.H.

    1981-01-01

    The radiographic pattern of nodular lmyphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases. (orig.)

  16. Distribution of Hydroxychloroquine in Lymphoid Tissue in a Rabbit Model for HIV Infection

    Science.gov (United States)

    González-Hernández, Iliana; Aguirre-Cruz, Lucinda; Sotelo, Julio; López-Arellano, Raquel; Morales-Hipólito, Adriana

    2014-01-01

    Hydroxychloroquine has been proposed for HIV treatment; however, little is known about its disposition in the lymphatic system, where replication takes place. Therefore, its distribution in lymphoid tissues (Peyer's patches and popliteal, submandibular, femoral, splenic, and prescapular lymph nodes) was evaluated and compared with that in blood. Results showed a high affinity of hydroxychloroquine for all of these tissues, with higher affinity for the splenic and submandibular lymph nodes, suggesting its potential use as a coadjuvant in HIV therapy. PMID:24145523

  17. Immunofluorescent staining of nuclear antigen in lymphoid cells transformed by Herpesvirus papio (HVP).

    Science.gov (United States)

    Schmitz, H

    1981-01-01

    An improved fixation method for antigen detection in lymphoblastoid cells is described. Herpesvirus papio nuclear antigen (HUPNA) could be stained in several transformed lymphoid cell lines by anti-complement immunofluorescence (ACIF). Antibody to HUPNA was detected in many human sera containing antibodies to Epstein-Barr virus capsid and nuclear antigen (EBNA). Rheumatoid arthritis sera showed a high incidence of both anti-EBNA and anti-HUPNA antibodies.

  18. High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation

    Directory of Open Access Journals (Sweden)

    Nancy H Ruddle

    2016-11-01

    Full Text Available High endothelial venules (HEVs and lymphatic vessels (LVs are essential for the function of the immune system, by providing communication between the body and lymph nodes (LNs, specialized sites of antigen presentation and recognition. HEVs bring in naïve and central memory cells and LVs transport antigen, antigen presenting cells, and lymphocytes in and out of LNs. Tertiary lymphoid organs (TLOs are accumulations of lymphoid and stromal cells that arise and organize at ectopic sites in response to chronic inflammation in autoimmunity, microbial infection, graft rejection, and cancer. TLOs are distinguished from primary lymphoid organs-the thymus and bone marrow, and secondary lymphoid organs (SLOs-the LNs, spleen, and Peyer’s patches, in that they arise in response to inflammatory signals, rather than in ontogeny. TLOs usually do not have a capsule, but are rather contained within the confines of another organ. Their structure, cellular composition, chemokine expression, and vascular and stromal support resemble SLOs and are the defining aspects of TLOs. T and B cells, antigen presenting cells, fibroblast reticular cells and other stromal cells and vascular elements including HEVs and LVs are all typical components of TLOS. A key question is whether the HEVs and LVs play comparable roles and are regulated similarly to those in LNs. Data are presented that support this concept, especially with regard to TLO HEVs. Emerging data suggest that the functions and regulation of TLO LVs are also similar to those in LNs. These observations support the concept that TLOs are not merely cellular accumulations, but are functional entities that provide sites to generate effector cells, and that their HEVs and LVs are crucial elements in those activities.

  19. 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

    2016-04-01

    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. 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. 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. 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. 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. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

    Science.gov (United States)

    Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne

    2016-11-01

    Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Identification of novel genes associated with renal tertiary lymphoid organ formation in aging mice.

    Science.gov (United States)

    Huang, Yuan; Caputo, Christina R; Noordmans, Gerda A; Yazdani, Saleh; Monteiro, Luiz Henrique; van den Born, Jaap; van Goor, Harry; Heeringa, Peter; Korstanje, Ron; Hillebrands, Jan-Luuk

    2014-01-01

    A hallmark of aging-related organ deterioration is a dysregulated immune response characterized by pathologic leukocyte infiltration of affected tissues. Mechanisms and genes involved are as yet unknown. To identify genes associated with aging-related renal infiltration, we analyzed kidneys from aged mice (≥20 strains) for infiltrating leukocytes followed by Haplotype Association Mapping (HAM) analysis. Immunohistochemistry revealed CD45+ cell clusters (predominantly T and B cells) in perivascular areas coinciding with PNAd+ high endothelial venules and podoplanin+ lymph vessels indicative of tertiary lymphoid organs. Cumulative cluster size increased with age (analyzed at 6, 12 and 20 months). Based on the presence or absence of clusters in male and female mice at 20 months, HAM analysis revealed significant associations with loci on Chr1, Chr2, Chr8 and Chr14 in male mice, and with loci on Chr4, Chr7, Chr13 and Chr14 in female mice. Wisp2 (Chr2) showed the strongest association (P = 5.00×10(-137)) in male mice; Ctnnbip1 (P = 6.42×10(-267)) and Tnfrsf8 (P = 5.42×10(-245)) (both on Chr4) showed the strongest association in female mice. Both Wisp2 and Ctnnbip1 are part of the Wnt-signaling pathway and the encoded proteins were expressed within the tertiary lymphoid organs. In conclusion, this study revealed differential lymphocytic infiltration and tertiary lymphoid organ formation in aged mouse kidneys across different inbred mouse strains. HAM analysis identified candidate genes involved in the Wnt-signaling pathway that may be causally linked to tertiary lymphoid organ formation.

  2. The Role of Radiotherapy in the Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

    OpenAIRE

    Nam, Taek-Keun; Ahn, Jae-Sook; Choi, Yoo-Duk; Jeong, Jae-Uk; Kim, Yong-Hyeob; Yoon, Mee Sun; Song, Ju-Young; Ahn, Sung-Ja; Chung, Woong-Ki

    2014-01-01

    Purpose To assess radiotherapy for patients with early stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma with respect to survival, treatment response, and complications. Materials and Methods Enrolled into this study were 48 patients diagnosed with gastric MALT lymphoma from January 2000 to September 2012. Forty-one patients had low grade and seven had mixed component with high grade. Helicobacter pylori eradication was performed in 33 patients. Thirty-four patients received rad...

  3. Characteristics of nasal-associated lymphoid tissue (NALT) and nasal absorption capacity in chicken.

    Science.gov (United States)

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2013-01-01

    As the main mucosal immune inductive site of nasal cavity, nasal-associated lymphoid tissue (NALT) plays an important role in both antigen recognition and immune activation after intranasal immunization. However, the efficiency of intranasal vaccines is commonly restricted by the insufficient intake of antigen by the nasal mucosa, resulting from the nasal mucosal barrier and the nasal mucociliary clearance. The distribution of NALT and the characteristic of nasal cavity have already been described in humans and many laboratory rodents, while data about poultry are scarce. For this purpose, histological sections of the chicken nasal cavities were used to examine the anatomical structure and histological characteristics of nasal cavity. Besides, the absorptive capacity of chicken nasal mucosa was also studied using the materials with different particle size. Results showed that the NALT of chicken was located on the bottom of nasal septum and both sides of choanal cleft, which mainly consisted of second lymphoid follicle. A large number of lymphocytes were distributed under the mucosal epithelium of inferior nasal meatus. In addition, there were also diffuse lymphoid tissues located under the epithelium of the concha nasalis media and the walls of nasal cavity. The results of absorption experiment showed that the chicken nasal mucosa was capable to absorb trypan blue, OVA, and fluorescent latex particles. Inactivated avian influenza virus (IAIV) could be taken up by chicken nasal mucosa except for the stratified squamous epithelium sites located on the forepart of nasal cavity. The intake of IAIV by NALT was greater than that of the nasal mucosa covering on non-lymphoid tissue, which could be further enhanced after intranasal inoculation combined with sodium cholate or CpG DNA. The study on NALT and nasal absorptive capacity will be benefit for further understanding of immune mechanisms after nasal vaccination and development of nasal vaccines for poultry.

  4. Lymphoid tissue neoplasms in the neck region - epidemiological and clinical analysis over 15 years.

    Science.gov (United States)

    Rzepakowska, Anna; Zwierzyńska, Klaudyna; Osuch-Wójcikiewicz, Ewa; Niemczyk, Kazimierz

    2017-06-30

    Epidemiological and clinical analysis of lymphoid tissue neoplasms in the neck region over a 15-year period. There was performed retrospective analysis of 97 patients, aged 17 to 88 years, mean age of 60.3 years. The analysis included data from subjective study, physical examination, image and histopathological studies Results: Almost all cases were lymphoid neoplasms - 95 patients (98%). B cell lymphoma was the most commonly diagnosed lymphoma - 74 cases (76%), followed by Hodgkin's lymphoma- 19 cases (20%). Only two patients had T-cell lymphoma (2%). There was observed prevalence among women, K: M ratio for the whole group was 51: 46, while male predominance was reported in Hodgkin's lymphoma patients (K: M = 7: 12). Over the 15-year period, there was an increase in the number of lymphoid tumors. The most common location on the neck were lymph nodes - 71 (73.2%). Extranodal localizations (26.8%) were most often associated with salivary glands: parotid and submandibular involvement and with the dominant lymphoma of the marginal zone MALT (14 cases). In 57% of patients the fine needle aspiration biopsy (FNAB) results were false, with positive results only in 32% of patients. Tumors from lymphoid tissue in the neck region are most commonly B-cell lymphomas or Hodgkin,s lymphomas. Non-specific clinical signs and non-specific radiological images, as well as non-diagnostic results o FNAB, make it difficult to effectively differentiate lymphomas with cancer metastasis in neck lymph nodes. Histopathology results of the excised lymph nodes remains a standard for lymphoma diagnosis.

  5. Identification and characterization of novel gut-associated lymphoid tissues in rat small intestine.

    Science.gov (United States)

    Hitotsumatsu, Osamu; Hamada, Hiromasa; Naganuma, Makoto; Inoue, Nagamu; Ishii, Hiromasa; Hibi, Toshifumi; Ishikawa, Hiromichi

    2005-10-01

    The crypt lamina propria of the mouse small intestine has been shown to harbor multiple tiny clusters filled with c-kit- and interleukin 7 receptor (IL-7R)-positive lympho-hemopoietic cells (cryptopatches; CPs). However, it has remained an open question whether similar lymphoid tissue are present in the gastrointesitinal tract in other animals. In the present study, we investigated whether the small intestine of rats harbored lymphoid tissues similar to mouse CPs. Immunohistochemical and flow cytometric analyses were carried out using various antibodies, including those to c-kit and IL-7R molecules. Lymphocyte-filled villi (LFVs), populated predominantly with c-kit- and IL-7 receptor (IL-7R)-positive cells and less with T cell receptor (TCR)-alphabeta T cells were found throughout the small intestine of young adult rats. Although LFVs were absent from fetal rat intestine, they were first detected at around 2 weeks after birth. Notably, in most LFVs that settled in the antimesenteric wall of the small intestine in young adult rats, immunoglobulin M-positive B cells were also detectable at the bottom of the LFVs. In aged rats, lymphocytes in some LFVs displayed a different phenotype, comprising a large B-cell area that included a germinal center. Thus, these clusters represent the first description of isolated lymphoid follicles (ILFs) in the rat small intestine. The present study provides the first evidence for c-kit- and IL-7R-positive lymphocyte clusters in the rat small intestine. Our data also indicating that LFVs and ILFs may constitute novel organized gut-associated lymphoid tissues in lamina propria of the rat small intestine.

  6. Bone marrow transplantation in aplastic anaemia using cyclophosphamide and total lymphoid irradiation

    International Nuclear Information System (INIS)

    Jansen, J.; Zwaan, F.E.; Noordijk, E.M.

    1980-01-01

    Six patients with severe aplastic anaemia received a bone-marrow graft after conditioning with cyclophosphamide and total lymphoid irradiation (TLI). No rejections occurred. Acute graft-versus-host disease developed in 3 patients and was fatal in one. Another patient died from systemic aspergillus infection. Chronic GVHD of the skin developed in a patient who was grafted with bone marrow from her HLA-phenotypically identical father. These data suggest that conditioning with cyclophosphamide and TLI is a promising regimen. (orig.) [de

  7. Identification of Cytological Features Distinguishing Mucosa-Associated Lymphoid Tissue Lymphoma from Reactive Lymphoid Proliferation Using Thyroid Liquid-Based Cytology

    Science.gov (United States)

    Suzuki, Ayana; Hirokawa, Mitsuyoshi; Ito, Aki; Takada, Nami; Higuchi, Miyoko; Hayashi, Toshitetsu; Kuma, Seiji; Miyauchi, Akira

    2018-01-01

    Objective To identify cytological differences between mucosa-associated lymphoid tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based cytology (LBC). Study Design We observed LBC and conventional specimens from 35 MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44 prominent nonneoplastic lymphocytic infiltration cases. Results In MALT-L cases, the incidence of lymphoglandular bodies in the LBC specimens was lower than that in the conventional specimens (p 10% of the lymphoid cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic infiltration also exhibited these findings. In LBC specimens, swollen naked nuclei with less punctate chromatin patterns and thin nuclear margins were observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic infiltration. Elongated nuclei were significantly more apparent in thyroid lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001), with a significantly higher incidence in LBC specimens than in conventional specimens (p < 0.001). Conclusions Lymphoglandular bodies are not reliable markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic lymphocytes in LBC specimens. PMID:29597203

  8. Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

    Science.gov (United States)

    Chu, Coco; Moriyama, Saya; Li, Zhi; Zhou, Lei; Flamar, Anne-Laure; Klose, Christoph S N; Moeller, Jesper B; Putzel, Gregory G; Withers, David R; Sonnenberg, Gregory F; Artis, David

    2018-06-26

    The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Identification of Cytological Features Distinguishing Mucosa-Associated Lymphoid Tissue Lymphoma from Reactive Lymphoid Proliferation Using Thyroid Liquid-Based Cytology.

    Science.gov (United States)

    Suzuki, Ayana; Hirokawa, Mitsuyoshi; Ito, Aki; Takada, Nami; Higuchi, Miyoko; Hayashi, Toshitetsu; Kuma, Seiji; Miyauchi, Akira

    2018-01-01

    To identify cytological differences between mucosa-associated lymphoid tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based cytology (LBC). We observed LBC and conventional specimens from 35 MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44 prominent nonneoplastic lymphocytic infiltration cases. In MALT-L cases, the incidence of lymphoglandular bodies in the LBC specimens was lower than that in the conventional specimens (p 10% of the lymphoid cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic infiltration also exhibited these findings. In LBC specimens, swollen naked nuclei with less punctate chromatin patterns and thin nuclear margins were observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic infiltration. Elongated nuclei were significantly more apparent in thyroid lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001), with a significantly higher incidence in LBC specimens than in conventional specimens (p < 0.001). Lymphoglandular bodies are not reliable markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic lymphocytes in LBC specimens. © 2018 The Author(s) Published by S. Karger AG, Basell.

  10. Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors

    International Nuclear Information System (INIS)

    Hanly, J.G.; Bresnihan, B.; Hassan, J.; Whelan, A.; Feighery, C.; Moriarty, M.

    1985-01-01

    Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The in-vitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. (author)

  11. Type two innate lymphoid cells; the Janus cells in health and disease

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-01-01

    Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

  12. Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis

    Directory of Open Access Journals (Sweden)

    Barbara C. Mindt

    2018-04-01

    Full Text Available Group 2 innate lymphoid cells (ILC2 represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

  13. 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.

  14. Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis.

    Science.gov (United States)

    Mindt, Barbara C; Fritz, Jörg H; Duerr, Claudia U

    2018-01-01

    Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

  15. Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

    Science.gov (United States)

    Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

    2017-10-01

    Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

  16. Type two innate lymphoid cells: the Janus cells in health and disease.

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Effect of thumus cell injections on germinal center formation in lymphoid tissues of nude (thymusless) mice

    International Nuclear Information System (INIS)

    Jacobson, E.B.; Caporale, L.H.; Thorbecke, G.J.

    1974-01-01

    Nude mice, partially backcrossed to Balb/c or DBA/2, were injected iv with 5 x 10 7 thymus cells from the respective inbred strain. The response of these mice to immunization with Brucella abortus antigen was studied, with respect to both antibody production and the formation of germinal centers in their lymphoid tissues. The results were compared to those obtained with nude mice to which no thymus cells were given, as well as to Balb/c, DBA/2, or +/question litter mate controls. Nude mice formed less 19S as well as 7S antibody than did litter mate controls and completely lacked germinal centers in lymph nodes and gut-associated lymphoid tissue. Those nude mice which had been injected with thymus cells made a much better secondary response, both for 19S and for 7S antibody, and had active germinal centers in their lymph nodes as early as 3 wk after thymus cell injection. Intestinal lymphoid tissue in nude mice showed only slight reconstitution of germinal center activity several months after thymus cell injection and none at earlier times. Irradiated (3000 R) thymus cells appeared as effective as normal cells in facilitating germinal center appearance and 7S antibody production in the nude mice

  18. In vivo confocal microscopy of conjunctiva-associated lymphoid tissue in healthy humans.

    Science.gov (United States)

    Agnifili, Luca; Mastropasqua, Rodolfo; Fasanella, Vincenzo; Di Staso, Silvio; Mastropasqua, Alessandra; Brescia, Lorenza; Mastropasqua, Leonardo

    2014-07-29

    To investigate modifications with aging of the presence, distribution and morphologic features of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects using laser scanning in vivo confocal microscopy (IVCM). A total of 108 (age range, 17-75 years) subjects were enrolled. In vivo confocal microscopy of the tarsal and bulbar conjunctiva, and impression cytology (IC) with CD3 (intra-epithelial T-lymphocytes) and CD20 (intra-epithelial B-lymphocytes) antibody immunofluorescence staining were performed. The main outcomes were subepithelial lymphocyte density (LyD), follicular density (FD), and follicular area (FA). The secondary outcomes were follicular reflectivity (FR), and lymphocyte density (FLyD), and CD3 and CD20 positivity. Conjunctiva-associated lymphoid tissue was observed in all subjects (97% only superior and 3% in both superior and inferior tarsum). Lymphocyte density ranged from 7.8 to 165.8 cells/mm(2) (46.42 [18.37]; mean [SD]), FD from 0.5 to 19.4 follicles/mm(2) (5.3 [3.6]), and FA from 1110 to 96,280 mm(2) (26,440 [26,280]). All three parameters showed a highly significant inverse cubic relationship with age (P lymphoid structures. These modifications may account for the decrease of mucosal immune response and increase of ocular surface diseases in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  19. Morphological and functional development of the interbranchial lymphoid tissue (ILT) in Atlantic salmon (Salmo salar L).

    Science.gov (United States)

    Dalum, Alf Seljenes; Griffiths, David James; Valen, Elin Christine; Amthor, Karoline Skaar; Austbø, Lars; Koppang, Erling Olaf; Press, Charles McLean; Kvellestad, Agnar

    2016-11-01

    The interbranchial lymphoid tissue (ILT) of Atlantic salmon originates from an embryological location that in higher vertebrates gives rise to both primary and secondary lymphoid tissues. Still much is unknown about the morphological and functional development of the ILT. In the present work a standardized method of organ volume determination was established to study its development in relation to its containing gill and the thymus. Based on morphological findings and gene transcription data, the ILT shows no signs of primary lymphoid function. In contrast to the thymus, an ILT-complex first became discernible after the yolk-sac period. After its appearance, the ILT-complex constitutes 3-7% of the total volume of the gill (excluding the gill arch) with the newly described distal ILT constituting a major part, and in adult fish it is approximately 13 times larger than the thymus. Confined regions of T-cell proliferation are present within the ILT. Communication with systemic circulation through the distal ILT is also highly plausible thus offering both internal and external recruitment of immune cells in the growing ILT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 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

  1. 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. PMID:27752256

  2. Detection of Mycobacterium avium subspecies in the gut associated lymphoid tissue of slaughtered rabbits.

    Science.gov (United States)

    Arrazuria, Rakel; Sevilla, Iker A; Molina, Elena; Pérez, Valentín; Garrido, Joseba M; Juste, Ramón A; Elguezabal, Natalia

    2015-06-11

    Rabbits are susceptible to infection by different species of the genus Mycobacterium. Particularly, development of specific lesions and isolation of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. paratuberculosis, both subspecies of the M. avium complex, has been reported in wildlife conditions. Although, rabbit meat production worldwide is 200 million tons per year, microbiological data on this source of meat is lacking and more specifically reports of mycobacterial presence in industrially reared rabbit for human consumption have not been published. To this end, we sought mycobacteria by microbiological and histopathological methods paying special attention to Mycobacterium avium subsp. paratuberculosis in rabbits from commercial rabbitries from the North East of Spain. M. avium subsp. paratuberculosis was not detected either by culture or PCR. However, Mycobacterium avium subsp. avium was detected in 15.15% (10/66) and Mycobacterium avium subsp. hominissuis was detected in 1.51% (1/66) of gut associated lymphoid tissue of sampled animals by PCR, whereas caecal contents were negative. 9% (6/66) of the animals presented gross lesions suggestive of lymphoid activation, 6% (4/66) presented granulomatous lesions and 3% (2/66) contained acid fast bacilli. Mycobacterial isolation from samples was not achieved, although colonies of Thermoactinomycetes sp. were identified by 16s rRNA sequencing in 6% (4/66) of sampled animals. Apparently healthy farmed rabbits that go to slaughter may carry M. avium subspecies in gut associated lymphoid tissue.

  3. Retinoic Acid Differentially Regulates the Migration of Innate Lymphoid Cell Subsets to the Gut.

    Science.gov (United States)

    Kim, Myung H; Taparowsky, Elizabeth J; Kim, Chang H

    2015-07-21

    Distinct groups of innate lymphoid cells (ILCs) such as ILC1, ILC2, and ILC3 populate the intestine, but how these ILCs develop tissue tropism for this organ is unclear. We report that prior to migration to the intestine ILCs first undergo a "switch" in their expression of homing receptors from lymphoid to gut homing receptors. This process is regulated by mucosal dendritic cells and the gut-specific tissue factor retinoic acid (RA). This change in homing receptors is required for long-term population and effector function of ILCs in the intestine. Only ILC1 and ILC3, but not ILC2, undergo the RA-dependent homing receptor switch in gut-associated lymphoid tissues. In contrast, ILC2 acquire gut homing receptors in a largely RA-independent manner during their development in the bone marrow and can migrate directly to the intestine. Thus, distinct programs regulate the migration of ILC subsets to the intestine for regulation of innate immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 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.

  5. Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection.

    Science.gov (United States)

    Yang, Lin; Tian, Zi-Bin; Yu, Ya-Nan; Zhang, Cui-Ping; Li, Xiao-Yu; Mao, Tao; Jing, Xue; Zhao, Wen-Jun; Ding, Xue-Li; Yang, Ruo-Ming; Zhang, Shuai-Qing

    2017-01-01

    Helicobacter suis has a greater tendency to induce gastric mucosa-associated lymphoid tissue lymphoma compared with other Helicobacter species in humans and animals. Saccharomyces boulardii has been established as an adjunct to H. pylori eradication treatment, but the effect of S. boulardii administration alone on Helicobacter infection remains unclear. Here, we found that S. boulardii administration effectively decreased the bacterial load of H. suis and inhibited the formation of lymphoid follicles in the stomach post-infection. The levels of H. suis-specific immunoglobulin A (IgA) and secretory IgA in the gastric juice and small intestinal secretions and the production of mouse β-defensin-3 in the small intestinal secretions were significantly increased by S. boulardii administration at 12 weeks after H. suis infection. In addition, feeding with S. boulardii inhibited the expression of inflammatory cytokines and lymphoid follicle formation-related factors after H. suis infection. These results suggested that S. boulardii may be useful for the prevention and treatment of Helicobacter infection-related diseases in humans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Recombinase, chromosomal translocations and lymphoid neoplasia: targeting mistakes and repair failures.

    Science.gov (United States)

    Marculescu, Rodrig; Vanura, Katrina; Montpellier, Bertrand; Roulland, Sandrine; Le, Trang; Navarro, Jean-Marc; Jäger, Ulrich; McBlane, Fraser; Nadel, Bertrand

    2006-09-08

    A large number of lymphoid malignancies is characterized by specific chromosomal translocations, which are closely linked to the initial steps of pathogenesis. The hallmark of these translocations is the ectopic activation of a silent proto-oncogene through its relocation at the vicinity of an active regulatory element. Due to the unique feature of lymphoid cells to somatically rearrange and mutate receptor genes, and to the corresponding strong activity of the immune enhancers/promoters at that stage of cell development, B- and T-cell differentiation pathways represent propitious targets for chromosomal translocations and oncogene activation. Recent progress in the understanding of the V(D)J recombination process has allowed a more accurate definition of the translocation mechanisms involved, and has revealed that V(D)J-mediated translocations result both from targeting mistakes of the recombinase, and from illegitimate repair of the V(D)J recombination intermediates. Surprisingly, V(D)J-mediated translocations turn out to be restricted to two specific sub-types of lymphoid malignancies, T-cell acute lymphoblastic leukemias, and a restricted set of mature B-cell Non-Hodgkin's lymphomas.

  7. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Juan Antonio Guadix

    2017-12-01

    Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

  8. Cellular therapy after spinal cord injury using neural progenitor cells

    NARCIS (Netherlands)

    Vroemen, Maurice

    2006-01-01

    In this thesis, the possibilities and limitations of cell-based therapies after spinal cord injury are explored. Particularly, the potential of adult derived neural progenitor cell (NPC) grafts to function as a permissive substrate for axonal regeneration was investigated. It was found that syngenic

  9. Progenitor cells in the kidney: biology and therapeutic perspectives

    NARCIS (Netherlands)

    Rookmaaker, M.B.; Verhaar, M.C.; Zonneveld, A.J. van; Rabelink, T.J.

    2004-01-01

    Progenitor cells in the kidney: Biology and therapeutic perspectives. The stem cell may be viewed as an engineer who can read the blue print and become the building. The role of this fascinating cell in physiology and pathophysiology has recently attracted a great deal of interest. The archetype of

  10. Long GRBs from binary stars: runaway, Wolf-Rayet progenitors

    NARCIS (Netherlands)

    Cantiello, M.; Yoon, S.C.; Langer, N.; Livio, M.

    2007-01-01

    The collapsar model for long gamma-ray bursts requires a rapidly rotating Wolf-Rayet star as progenitor. We test the idea of producing rapidly rotating Wolf-Rayet stars in massive close binaries through mass accretion and consecutive quasi-chemically homogeneous evolution — the latter had previously

  11. Long GRBs from Binary Stars: Runaway, Wolf-Rayet Progenitors

    NARCIS (Netherlands)

    Cantiello, M.; Yoon, S.C.; Langer, N.; Livio, M.

    2007-01-01

    The collapsar model for long gamma-ray bursts requires a rapidly rotating Wolf-Rayet star as progenitor. We test the idea of producing rapidly rotating Wolf-Rayet stars in massive close binaries through mass accretion and consecutive quasi-chemically homogeneous evolution - the latter had previously

  12. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

    DEFF Research Database (Denmark)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir

    2015-01-01

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory m...

  13. Intersections of lung progenitor cells, lung disease and lung cancer.

    Science.gov (United States)

    Kim, Carla F

    2017-06-30

    The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

  14. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    NARCIS (Netherlands)

    Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert

    2017-01-01

    Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA)

  15. Mobilization of hematopoietic stem and progenitor cells in mice

    NARCIS (Netherlands)

    Robinson, Simon N; van Os, Ronald P; Bunting, Kevin

    2008-01-01

    Animal models have added significantly to our understanding of the mechanism(s) of hematopoietic stem and progenitor cell (HSPC) mobilization. Such models suggest that changes in the interaction between the HSPC and the hematopoietic microenvironmental 'niche' (cellular and extracellular components)

  16. Endothelial progenitor cell-based neovascularization : implications for therapy

    NARCIS (Netherlands)

    Krenning, Guido; van Luyn, Marja J. A.; Harmsen, Martin C.

    Ischemic cardiovascular events are a major cause of death globally. Endothelial progenitor cell (EPC)-based approaches can result in improvement of vascular perfusion and might offer clinical benefit. However, although functional improvement is observed, the lack of long-term engraftment of EPCs

  17. The progenitor of Nova Cygni 2006 (=V2362 Cyg)

    NARCIS (Netherlands)

    Steeghs, D.; Greimel, R.; Drew, J.; Irwin, M.; Gaensicke, B.; Groot, P.J.; Knigge, C.

    2006-01-01

    We report on the detection of the likely progenitor to Nova Cygni 2006 = V2362 Cyg (IAUC #8697, #8698, ATel #792) using images from the INT Photometric H-Alpha Survey (IPHAS; http://www.iphas.org). The field containing the classical nova was observed as part of our galactic plane survey on Aug. 3rd

  18. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Klassen, Henry

    2006-01-01

    We evaluated the host response to murine retinal progenitor cells (RPCs) following transplantation to the subretinal space (SRS) of the pig. RPCs from GFP mice were transplanted subretinally in 18 nonimmunosuppressed normal or laser-treated pigs. Evaluation of the SRS was performed on hematoxylin-eosin...

  19. Mass ejection in failed supernovae: variation with stellar progenitor

    Science.gov (United States)

    Fernández, Rodrigo; Quataert, Eliot; Kashiyama, Kazumi; Coughlin, Eric R.

    2018-05-01

    We study the ejection of mass during stellar core-collapse when the stalled shock does not revive and a black hole forms. Neutrino emission during the protoneutron star phase causes a decrease in the gravitational mass of the core, resulting in an outward going sound pulse that steepens into a shock as it travels out through the star. We explore the properties of this mass ejection mechanism over a range of stellar progenitors using spherically symmetric, time-dependent hydrodynamic simulations that treat neutrino mass-loss parametrically and follow the shock propagation over the entire star. We find that all types of stellar progenitor can eject mass through this mechanism. The ejected mass is a decreasing function of the surface gravity of the star, ranging from several M⊙ for red supergiants to ˜0.1 M⊙ for blue supergiants and ˜10-3 M⊙ for Wolf-Rayet stars. We find that the final shock energy at the surface is a decreasing function of the core-compactness, and is ≲ 1047-1048 erg in all cases. In progenitors with a sufficiently large envelope, high core-compactness, or a combination of both, the sound pulse fails to unbind mass. Successful mass ejection is accompanied by significant fallback accretion that can last from hours to years. We predict the properties of shock breakout and thermal plateau emission produced by the ejection of the outer envelope of blue supergiant and Wolf-Rayet progenitors in otherwise failed supernovae.

  20. Hmga2 regulates self-renewal of retinal progenitors.

    Science.gov (United States)

    Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

    2014-11-01

    In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

  1. Intersections of lung progenitor cells, lung disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Carla F. Kim

    2017-06-01

    Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

  2. Characteristics of meniscus progenitor cells migrated from injured meniscus.

    Science.gov (United States)

    Seol, Dongrim; Zhou, Cheng; Brouillette, Marc J; Song, Ino; Yu, Yin; Choe, Hyeong Hun; Lehman, Abigail D; Jang, Kee W; Fredericks, Douglas C; Laughlin, Barbara J; Martin, James A

    2017-09-01

    Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous stem/progenitor cells has emerged as a promising new strategy. We showed previously that migratory chondrogenic progenitor cells (CPCs) were recruited to injured cartilage, where they showed a capability in situ tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells. Explant studies revealed that migrating cells were mainly confined to the red zone in normal menisci: However, these cells were capable of repopulating defects made in the white zone. In vivo, migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. Gene expression profiling showed that the migrating population was more similar to CPCs than other meniscus cells. Finally, migrating cells equaled CPCs in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1966-1972, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  3. TYPE IIb SUPERNOVAE WITH COMPACT AND EXTENDED PROGENITORS

    International Nuclear Information System (INIS)

    Chevalier, Roger A.; Soderberg, Alicia M.

    2010-01-01

    The classic example of a Type IIb supernova is SN 1993J, which had a cool extended progenitor surrounded by a dense wind. There is evidence for another category of Type IIb supernova that has a more compact progenitor with a lower density, probably fast, wind. Distinguishing features of the compact category are weak optical emission from the shock heated envelope at early times, nonexistent or very weak H emission in the late nebular phase, rapidly evolving radio emission, rapid expansion of the radio shell, and expected nonthermal as opposed to thermal X-ray emission. Type IIb supernovae that have one or more of these features include SNe 1996cb, 2001ig, 2003bg, 2008ax, and 2008bo. All of these with sufficient radio data (the last four) show evidence for presupernova wind variability. We estimate a progenitor envelope radius ∼1 x 10 11 cm for SN 2008ax, a value consistent with a compact Wolf-Rayet progenitor. Supernovae in the SN 1993J extended category include SN 2001gd and probably the Cas A supernova. We suggest that the compact Type IIb events be designated Type cIIb and the extended ones Type eIIb. The H envelope mass dividing these categories is ∼0.1 M sun .

  4. Cardiac stem/progenitor cells, secreted proteins, and proteomics

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Abraham, M.R.; Van Eyk, J.E.

    2009-01-01

    Roč. 583, č. 11 (2009), s. 1800-1807 ISSN 0014-5793 Institutional research plan: CEZ:AV0Z40310501 Keywords : Cardiac stem/progenitor cell * paracrine factor * secretome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.541, year: 2009

  5. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Jing Song

    2018-03-01

    Full Text Available A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG, a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133+ and CD133− cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133+ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet. αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  6. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation.

    Science.gov (United States)

    Song, Jing; Ma, Dongshen; Xing, Yun; Tang, Shanshan; Alahdal, Murad; Guo, Jiamin; Pan, Yi; Zhang, Yanfeng; Shen, Yumeng; Wu, Qiong; Lu, Zhou; Jin, Liang

    2018-03-22

    A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133⁺ and CD133 - cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133⁺ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.

  7. [Stem and progenitor cells in biostructure of blood vessel walls].

    Science.gov (United States)

    Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

    2013-09-18

    Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  8. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  9. Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Gene-Errol E Ringpis

    Full Text Available Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against HIV-1 in patients. Using the humanized bone marrow/liver/thymus (hu-BLT mouse model which allows investigation of human hematopoietic stem/progenitor cell (HSPC transplant and immune system reconstitution as well as HIV-1 infection, we previously demonstrated stable inhibition of CCR5 expression in systemic lymphoid tissues via transplantation of HSPCs genetically modified by lentiviral vector transduction to express short hairpin RNA (shRNA. However, CCR5 down-regulation will not be effective against existing CXCR4-tropic HIV-1 and emergence of resistant viral strains. As such, combination approaches targeting additional steps in the virus lifecycle are required. We screened a panel of previously published shRNAs targeting highly conserved regions and identified a potent shRNA targeting the R-region of the HIV-1 long terminal repeat (LTR. Here, we report that human CD4(+ T-cells derived from transplanted HSPC engineered to co-express shRNAs targeting CCR5 and HIV-1 LTR are resistant to CCR5- and CXCR4- tropic HIV-1-mediated depletion in vivo. Transduction with the combination vector suppressed CXCR4- and CCR5- tropic viral replication in cell lines and peripheral blood mononuclear cells in vitro. No obvious cytotoxicity or interferon response was observed. Transplantation of combination vector-transduced HSPC into hu-BLT mice resulted in efficient engraftment and subsequent stable gene marking and CCR5 down-regulation in human CD4(+ T-cells within peripheral blood and systemic lymphoid tissues, including gut-associated lymphoid tissue, a major site of robust viral replication, for over twelve weeks. CXCR4- and CCR5- tropic HIV-1 infection was effectively inhibited in hu-BLT mouse spleen-derived human CD4(+ T-cells ex vivo. Furthermore, levels of gene-marked CD4(+ T-cells in peripheral blood increased despite systemic infection with either

  10. Efficacy of total lymphoid irradiation for chronic allograft rejection following double lung transplantation

    International Nuclear Information System (INIS)

    Diamond, David A.; Michalski, Jeff M.; Trulock, Elbert M.; Lynch, John P.

    1997-01-01

    Purpose: The purpose of this study was to assess the safety and efficacy of total lymphoid irradiation in a series of patients experiencing chronic rejection following bilateral lung transplantation. Patients and Materials: Eleven patients (10 males, 1 female) received total lymphoid irradiation for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Treatment was delivered between March, 1995, and September, 1996. Mean patient age was 33 years (range 15-51). Indications for transplantation included cystic fibrosis (7 patients), alpha 1 anti-trypsin deficiency (2 patients), primary pulmonary hypertension (1 patient), and emphysema (1 patient). Radiation therapy was prescribed as 800 cGy delivered in ten 80 cGy fractions, 2 fractions per week, via AP/PA mantle and inverted-Y fields. Radiation was withheld for total wbc count 3 , absolute neutrophil count 3 , or platelets 3 . Serial pre- and post-radiation therapy pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements (use of methylprednisolone, azathioprine, mycophenolate mofetil, OKT3, and FK506) were monitored. Results: In the 3 months preceding total lymphoid irradiation, the average decrease in FEV 1 was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). At initiation of radiation therapy, the average FEV 1 was 1.4 liters (range 0.77-2.28). Only (4(11)) patients completed all 10 treatment fractions. Reasons for discontinuation included unabated rejection (4 patients), worsening pulmonary infection (2 patients), and persistent thrombocytopenia (1 patient). No treatment course was discontinued because of persistent neutropenia or leukopenia. Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related donor transplants. He is alive and well. Six patients died. Two of these deaths were due

  11. Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis

    Directory of Open Access Journals (Sweden)

    Samira Chabab

    2016-01-01

    Full Text Available The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.

  12. PROGENITOR-EXPLOSION CONNECTION AND REMNANT BIRTH MASSES FOR NEUTRINO-DRIVEN SUPERNOVAE OF IRON-CORE PROGENITORS

    Energy Technology Data Exchange (ETDEWEB)

    Ugliano, Marcella; Janka, Hans-Thomas; Marek, Andreas [Max-Planck-Institut fuer Astrophysik, Karl-Schwarzschild-Str. 1, D-85748 Garching (Germany); Arcones, Almudena [Institut fuer Kernphysik, Technische Universitaet Darmstadt, Schlossgartenstr. 2, D-64289 Darmstadt (Germany)

    2012-09-20

    We perform hydrodynamic supernova (SN) simulations in spherical symmetry for over 100 single stars of solar metallicity to explore the progenitor-explosion and progenitor-remnant connections established by the neutrino-driven mechanism. We use an approximative treatment of neutrino transport and replace the high-density interior of the neutron star (NS) by an inner boundary condition based on an analytic proto-NS core-cooling model, whose free parameters are chosen such that explosion energy, nickel production, and energy release by the compact remnant of progenitors around 20 M{sub Sun} are compatible with SN 1987A. Thus, we are able to simulate the accretion phase, initiation of the explosion, subsequent neutrino-driven wind phase for 15-20 s, and the further evolution of the blast wave for hours to days until fallback is completed. Our results challenge long-standing paradigms. We find that remnant mass, launch time, and properties of the explosion depend strongly on the stellar structure and exhibit large variability even in narrow intervals of the progenitors' zero-age main-sequence mass. While all progenitors with masses below {approx}15 M{sub Sun} yield NSs, black hole (BH) as well as NS formation is possible for more massive stars, where partial loss of the hydrogen envelope leads to weak reverse shocks and weak fallback. Our NS baryonic masses of {approx}1.2-2.0 M{sub Sun} and BH masses >6 M{sub Sun} are compatible with a possible lack of low-mass BHs in the empirical distribution. Neutrino heating accounts for SN energies between some 10{sup 50} erg and {approx}2 Multiplication-Sign 10{sup 51} erg but can hardly explain more energetic explosions and nickel masses higher than 0.1-0.2 M{sub Sun }. These seem to require an alternative SN mechanism.

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

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    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. Single progenitor model for GW150914 and GW170104

    Science.gov (United States)

    D'Orazio, Daniel J.; Loeb, Abraham

    2018-04-01

    The merger of stellar-mass black holes (BHs) is not expected to generate detectable electromagnetic (EM) emission. However, the gravitational wave (GW) events GW150914 and GW170104, detected by the Laser Interferometer Gravitational Wave Observatory to be the result of merging, ˜60 M⊙ binary black holes (BBHs), each have claimed coincident gamma-ray emission. Motivated by the intriguing possibility of an EM counterpart to BBH mergers, we construct a model that can reproduce the observed EM and GW signals for GW150914- and GW170104-like events, from a single-star progenitor. Following Loeb [Astrophys. J. Lett. 819, L21 (2016), 10.3847/2041-8205/819/2/L21], we envision a massive, rapidly rotating star within which a rotating-bar instability fractures the core into two overdensities that fragment into clumps which merge to form BHs in a tight binary with arbitrary spin-orbit alignment. Once formed, the BBH inspirals due to gas and gravitational-wave drag until tidal forces trigger strong feeding of the BHs with the surrounding stellar-density gas about 10 sec before merger. The resulting giga-Eddington accretion peak launches a jet that breaks out of the progenitor star and drives a powerful outflow that clears the gas from the orbit of the binary within 1 sec, preserving the vacuum GW waveform in the Laser Interferometer Gravitational Wave Observatory band. The single-progenitor scenario predicts the existence of variability of the gamma-ray burst, modulated at the ˜0.2 sec chirping period of the BBH due to relativistic Doppler boost. The jet breakout should be accompanied by a low-luminosity supernova. Finally, because the BBHs of the single-progenitor model do not exist at large separations, they will not be detectable in the low-frequency gravitational-wave band of the Laser Interferometer Space Antenna. Hence, the single-progenitor BBHs will be unambiguously discernible from BBHs formed through alternate, double-progenitor evolution scenarios.

  15. La violencia de hijos adolescentes contra sus progenitores La violencia de hijos adolescentes contra sus progenitores

    Directory of Open Access Journals (Sweden)

    Concepción Aroca Montolío

    2013-10-01

    Full Text Available According to Prosecutor’s Office of the Minor, the accusation interposed by mothers and/or fathers victims by theirs children, along 2007 were 2603, in 2008 amounted 4.211, in 2009 there were 5.209 and in 2010 there were 8.000 accusations. Suede this worrying increase, the principal aim of our article is to check the scientific international and national documentation, from 1957 until the year 2010 that analyses the phenomenon of the adolescent violence against parents, to achieve an approximation to its keys that there allows us the comprehension and analysis of this serious familiar problem. For it we will analyse: (a the importance of this crime by means of criminological mediators: prevalence and incidence; (b the age and sex variables’ aggressors to be able to establish a basic profile about theirs and, (c the violence types that the teenagers wield to damage, prejudice and suffering against their progenitors, with the aim to obtain what they want. The information obtained in this research review and qualitative analysis, change in base to the methodology used and the type of sample under study to obtain conclusions. Even though, we wantto do research into needs to investigate this type of familiar violence, and from there, to do researches with rigorous scientific methodologies, unifying criteria and variables to be investigating, to be able to anticipate in this increasing problem that the parents have. Según la Fiscalía del Menor en el año 2007, las denuncias interpuestas por madres y/o padres, víctimas de malos tratos por sus hijos e hijas menores de edad, fueron 2.683. En 2008 ascendieron a 4.211, en 2009 se presentaron 5.209 y en el año 2010 se registraron 8.000 denuncias. Ante éste preocupante incremento, el objetivo principal de nuestro artículo es revisar la documentación científica que analiza la violencia filio-parental,  desde 1957 hasta el año 2011, para lograr una aproximación a sus claves que nos permita la

  16. Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996-2004.

    Science.gov (United States)

    Carreon, J Daniel; Morton, Lindsay M; Devesa, Susan S; Clarke, Christina A; Gomez, Scarlett L; Glaser, Sally L; Sakoda, Lori C; Linet, Martha S; Wang, Sophia S

    2008-12-01

    To establish baseline data for lymphoid neoplasm incidence by subtype for six Asian-American ethnic groups. Incident rates were estimated by age and sex for six Asian ethnic groups--Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese--in five United States cancer registry areas during 1996-2004. For comparison, rates for non-Hispanic Whites were also estimated. During 1996-2004, Filipinos had the highest (24.0) and Koreans had the lowest incidence (12.7) of total lymphoid neoplasms. By subtype, Vietnamese and Filipinos had the highest incidence for diffuse large B-cell lymphoma (DLBCL) (8.0 and 7.2); Japanese had the highest incidence of follicular lymphoma (2.3). Although a general male predominance of lymphoid neoplasms was observed, this pattern varied by lymphoid neoplasm subtype. Whites generally had higher rates than all Asian ethnic groups for all lymphoid neoplasms and most lymphoma subtypes, although the magnitude of the difference varied by both ethnicity and lymphoma subtype. The observed variations in incidence patterns among Asian ethnic groups in the United States suggest that it may be fruitful to pursue studies that compare Asian populations for postulated environmental and genetic risk factors.

  17. Progenitors of type Ia supernovae in elliptical galaxies

    International Nuclear Information System (INIS)

    Gilfanov, M.; Bogdan, A.

    2011-01-01

    Although there is a nearly universal agreement that type Ia supernovae are associated with the thermonuclear disruption of a CO white dwarf, the exact nature of their progenitors is still unknown. The single degenerate scenario envisages a white dwarf accreting matter from a non-degenerate companion in a binary system. Nuclear energy of the accreted matter is released in the form of electromagnetic radiation or gives rise to numerous classical nova explosions prior to the supernova event. We show that combined X-ray output of supernova progenitors and statistics of classical novae predicted in the single degenerate scenario are inconsistent with X-ray and optical observations of nearby early type galaxies and galaxy bulges. White dwarfs accreting from a donor star in a binary system and detonating at the Chandrasekhar mass limit can account for no more than ∼5% of type Ia supernovae observed in old stellar populations.

  18. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    Directory of Open Access Journals (Sweden)

    Silvia Consalvi

    2016-01-01

    Full Text Available In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD.

  19. Glial progenitor cell-based treatment of the childhood leukodystrophies

    DEFF Research Database (Denmark)

    Osório, M. Joana; Goldman, Steven A.

    2016-01-01

    stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group...... genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease....... and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent...

  20. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

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    Alerie Guzman De La Fuente

    2017-08-01

    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.