Articles de revues : « Non-lymphoid organs »

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Jandrić-Kočić, Marijana. « Recirculation of naive T lymphocytes ». Medicinski glasnik Specijalne bolnice za bolesti štitaste žlezde i bolesti metabolizma 27, n^o 86 (2022) : 25–48. http://dx.doi.org/10.5937/mgiszm2286025j.

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After development in the thymus, naive T lymphocytes come into circulation and continuously recirculate between the blood and peripheral lymphoid organs for activation and transformation into effector cells. The movement of naive T lymphocytes represents an ordered sequence controlled by the expression of specific of specific proteins (selectin, integrin and chemokine) that includes the recruitment of circulating lymphocytes on the luminal surface of the blood vessel, transendothelial transition and migration within the extravascular compartment of peripheral lymphoid organs. The question of the movement of naive T lymphocytes in and out of non-lymphoid organs in physiological conditions has not been fully resolved. There is an opinion that naive T lymphocytes under physiological conditions routinely access almost all non-lymphoid organs for the purpose of immunosurveillance and/or tolerance induction. Non-lymphoid organs burdened by chronic inflammation and tumor processes may possess a significant number of naive T lymphocytes. Organized lymphoid tissue causally contributes to the persistence of certain autoimmune diseases. Recruitment in tumor tissue and subsequent antitumor immune response correspond with a positive prognosis.

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Parker, George A., et Catherine A. Picut. « Immune Functioning in Non lymphoid Organs : The Liver ». Toxicologic Pathology 40, n^o 2 (16 novembre 2011) : 237–47. http://dx.doi.org/10.1177/0192623311428475.

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Feizi, Neda, Neda Feizi, Gang Zhang, Latha Halesha, Khodor Abou Daya et Martin H. Oberbarnscheidt. « Tertiary Lymphoid Organs promote allograft rejection ». Journal of Immunology 212, n^o 1_Supplement (1 mai 2024) : 0321_5062. http://dx.doi.org/10.4049/jimmunol.212.supp.0321.5062.

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Abstract Tertiary lymphoid organs (TLOs) are ectopic lymphoid structures that arise in non-lymphoid tissues and are frequently observed in tissue affected by non-resolving chronic inflammation. If TLOs are beneficial or detrimental in transplantation is controversial. We investigate the role of TLO and LTbR in transplantation by manipulating the LTa-LTbR pathway. Using a mouse allo kidney transplantation model, we found that preformed intragraft TLO are sufficient to precipitate rejection in recipients lacking all secondary lymphoid organs (SLO)(LTbRko). In WT recipients with a complete set of SLO, intragraft TLO accelerated rejection (MST=63 vs. 225 d). Donor grafts that cannot form TLO (LTbRko) prolonged allograft survival (MST 24 vs 11 d) in an acute kidney rejection model. Intravital imaging confirmed that T and B cell activation takes place in renal TLO upon migration of naïve T and B cells and prolonged interactions with dendritic cells. T cells produced IFNg and Confetti+/+ B cells clonally expanded within TLO. In summary, intragraft TLO are sufficient for and accelerate allograft rejection. Local immune responses are initiated and maintained in intragraft TLO, while disruption of TLO formation in the allograft leads to prolonged allograft survival. TLO support T and B cell activation as well as local DSA formation. These findings highlight the importance of TLO in local immune responses with implications for cancer, autoimmunity and transplantation.

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Weninger, Wolfgang, Maté Biro et Rohit Jain. « Leukocyte migration in the interstitial space of non-lymphoid organs ». Nature Reviews Immunology 14, n^o 4 (7 mars 2014) : 232–46. http://dx.doi.org/10.1038/nri3641.

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Preziuso, S., GE Magi, S. Mari et G. Renzoni. « Detection of Visna Maedi virus in mesenteric lymph nodes and in other lymphoid tissues of sheep three years after respiratory infection ». Veterinární Medicína 58, No. 7 (20 août 2013) : 359–63. http://dx.doi.org/10.17221/6916-vetmed.

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Visna/Maedi virus (VMV), a small ruminant lentivirus responsible for lymphoproliferative pneumonia, encephalitis, arthritis and/or mastitis in sheep, has been detected in different non-lymphoid organs. However, only a few investigations have been carried out in lymphoid tissues. In this study, some lymphoid tissues and lymph node draining or non-draining VMV target organs from five sheep infected experimentally by the respiratory route three years previously were investigated. Archival samples of spleen, red bone marrow, caudal mediastinal lymph nodes, mammary lymph nodes, popliteal lymph nodes and mesenteric lymph nodes were tested by PCR for the presence of proviral DNA. Popliteal and mesenteric lymph node samples were tested also by immunohistochemical staining of the viral capsid antigen p28. The proviral DNA was detected by PCR in all the lymphoid tissue samples from the infected sheep. The viral antigen was stained in mononuclear cells in popliteal and mesenteric lymph nodes of the infected sheep. Although the lymph nodes draining the classical target organs seem to be more infected than the others, both the viral capsid antigen and the proviral DNA were present also in lymph nodes draining non-target organs, such as the mesenteric lymph nodes. These findings show the presence of VMV in different lymphoid tissues in the late stages of infection and suggest a potential role of these tissues as a site for viral reservoir and replication, even three years after infection.  

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Tkachev, Victor, Scott Nicholas Furlan, E. Lake Potter, Betty H. Zheng, Daniel J. Hunt, Lucrezia Colonna, Agne Taraseviciute et al. « Delineating tissue-specific alloimmunity during acute GVHD ». Journal of Immunology 200, n^o 1_Supplement (1 mai 2018) : 55.1. http://dx.doi.org/10.4049/jimmunol.200.supp.55.1.

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Abstract After allogeneic hematopoietic cell transplantation (allo-HCT), donor T cells undergo priming in secondary lymphoid tissues followed by migration to different target organs, where they mediate inflammation and cause acute Graft-versus-Host Disease (aGVHD). Here, we characterized T cells infiltrating GVHD-target organs using a model of aGVHD in non-human primates in order to delineate tissue-specific patterns of the alloimmune response. We found that aGVHD profoundly shifted the T cell phenotype from the naïve state toward an effector-memory state in both the blood and secondary lymphoid organs, with an attenuated shift in non-lymphoid organs. However, in all compartments, tissue-infiltrating T cells demonstrated an aGVHD-specific activated phenotype characterized by a high rate of proliferation and elevated effector functions. In addition, transcriptomic profiles of aGVHD- and tissue-residency developed in T cells residing the colon, liver and lungs as well as in the blood. To further delineate the patterns of T cell trafficking and activation during aGVHD, we directly labeled leukocytes in vivo using fluorescent anti-CD45 antibodies. Using this approach, we detected notable changes in T cell trafficking patterns which included increased T cell trafficking to lymph nodes, lungs and kidneys after allo-HCT, with rates of T cell migration to the GI tract unchanged even during aGVHD. These data provides novel insights into the spatial organization of systemic alloimmunity during aGVHD and the organ-specific impact of this disease on T cell trafficking, activation and functional maturation.

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Hotchkiss, R., M. Hiramatsu, P. Cobb, T. Buchman et I. Karl. « CECAL LIGATION AND PUNCTURE (CLP) IN MICE TRIGGERS APOPTOSIS IN LYMPHOID AND NON-LYMPHOID ORGANS. » Shock 5 (juin 1996) : 71. http://dx.doi.org/10.1097/00024382-199606002-00226.

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Jia, Cunxin, Yujie Zhou, Xiaohuan Huang, Xi Peng, Linyan Liu, Linyan Zhou, Li Jin, Hongjuan Shi, Jing Wei et Deshou Wang. « The cellular protein expression of Foxp3 in lymphoid and non-lymphoid organs of Nile tilapia ». Fish & ; Shellfish Immunology 45, n^o 2 (août 2015) : 300–306. http://dx.doi.org/10.1016/j.fsi.2015.03.021.

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Finke, Daniela, et Hans Acha-Orbea. « Differential migration ofin vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs ». European Journal of Immunology 31, n^o 9 (septembre 2001) : 2603–11. http://dx.doi.org/10.1002/1521-4141(200109)31:9<2603 ::aid-immu2603>3.0.co;2-8.

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Sainova, Iskra, Vera Kolyovska, Desislava Drenska, Dimitar Maslarov, Andrey Petrov, Dimitrina Dimitrova-Dikanarova et Tzvetanka Markova. « Production of anti-GM3, anti-GM1, and anti-GD1A antibodies by non-lymphoid cells, tissues, and organs ». Pharmacia 71 (1 novembre 2024) : 1–8. http://dx.doi.org/10.3897/pharmacia.71.e138022.

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Gangliosides are acidic glycosphingolipids localized mainly on the outer membrane layer of the membranous cell structures. These molecules participate in important mechanisms at molecular, cellular, tissue, organ, and organism levels. It has been proven that gangliosides play a role as regulators of various biological processes but also as markers in a number of multifactor pathologies. In this regard, the present study determined the titers of the GM3, GM1, and GD1a gangliosides, as well as the titers of IgG-class antibodies against each of them by enzyme-linked immunosorbent assay (ELISA), in several different anatomic organs: brain, pancreas, myocardium, liver, and small intestine from rodents. A total extract (control sample) containing the complete set of molecules is prepared from each isolated anatomic organ. An equivalent amount of the extract is passed through a GSH-agarose column in order to select the molecules from each organ possessing affinity to the reduced form of glutathione tripeptide (GSH). GSH is known as an antioxidant, immunomodulator, cardioprotector, neuroprotector, hepatoprotector, anticancer, and antiaging agent. As a whole, significantly lower titers of the three gangliosides and the antibodies to them are reported in the myocardium and liver samples compared to the brain and pancreas samples. Taking into account that the myocardium and liver are the organs known with the highest content of GSH, the obtained results can be explained by the possibly high content of free and/or newly synthesized GSH in them, which does not participate in intermolecular interactions compared to the other investigated organs. Complete absence of each of the three tested gangliosides or of antibodies against them at certain dilutions of the small intestine samples, as well as the highest titers of the same parameters compared to the corresponding samples from the other organs of each of the gangliosides or of the specific antibodies at other dilutions, is observed. One of the explanations for those peculiarities is associated with the presence of the intestinal microflora, including the influence of intestinal bacteria neuraminidases (sialidases). The presented data also show a possibility of antibodies/immunoglobulins production by non-lymphoid cells, tissues, and organs in suitable conditions. Since the immunoglobulins thus produced reside outside the germinal centers of the specialized lymphoid tissues and organs, regulation of their production and functions by interactions with small ions and/or molecules is also important. Gangliosides are namely such small molecules. Special attention is paid to intermolecular interactions involving the listed gangliosides and GSH. The main objective is related to understanding the mechanisms underlying the interaction between the individual organs and systems in the body.

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Duijvestijn, A. M., M. Kerkhove, R. F. Bargatze et E. C. Butcher. « Lymphoid tissue- and inflammation-specific endothelial cell differentiation defined by monoclonal antibodies. » Journal of Immunology 138, n^o 3 (1 février 1987) : 713–19. http://dx.doi.org/10.4049/jimmunol.138.3.713.

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Abstract Endothelial cells play an essential role in immune responses by regulating the entry of leukocytes into lymphoid tissues and sites of inflammation. As an initial approach to analyzing endothelial cell specialization in relation to such immune function, we have produced monoclonal antibodies (MAB) against mouse lymph node endothelium. Three antibodies were selected: MECA-20, recognizing the endothelium of all blood vessels in lymphoid as well as non-lymphoid organs; MECA-217, which stains the endothelium lining large elastic arteries, but among small vessels is specific for post-capillary venules within lymphoid organs and tissues exposed to exogenous antigen, such as skin and uterus; and MECA-325, an antibody that demonstrates specificity for the specialized high endothelial venules (HEV) that control lymphocyte homing into lymph nodes and Peyer's patches. MECA-325 failed to stain vessels in any non-lymphoid organs tested. Immunoperoxidase studies of HEV in lymph node frozen sections, and of isolated high endothelial cells in suspensions, demonstrated that the antigens recognized by all three antibodies are expressed at the cell surface; those defined by MECA-20 and MECA-325 are also present in the cytoplasm. To study the regulation of the antigens defined by these MAB in relation to extra-lymphoid immune reactions, we assessed their expression in induced s.c. granulomas as a model for chronic inflammation. Small vessels in the granulomas were already stained by MECA-217 in the first days of development. In contrast MECA-325 detected postcapillary venules (which frequently displayed the morphologic characteristics of HEV) only from approximately 1 wk, in parallel with the development of a persistent mononuclear cell infiltrate including numerous lymphocytes. The selective appearance of the MECA-325 antigen on vascular endothelium supporting lymphocyte traffic in both lymphoid and extra-lymphoid sites suggests that this antigen may play an important role in the process of lymphocyte extravasation. The demonstration of lymphoid organ- and inflammation-specific microvascular antigens offers direct evidence for a complex specialization of endothelium in relation to immune stimuli, and supports the concept that microvascular differentiation may play an important role in local immune responses.

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Műzes, Györgyi, Bettina Bohusné Barta et Ferenc Sipos. « Colitis and Colorectal Carcinogenesis : The Focus on Isolated Lymphoid Follicles ». Biomedicines 10, n^o 2 (21 janvier 2022) : 226. http://dx.doi.org/10.3390/biomedicines10020226.

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Gut-associated lymphoid tissue is one of the most diverse and complex immune compartments in the human body. The subepithelial compartment of the gut consists of immune cells of innate and adaptive immunity, non-hematopoietic mesenchymal cells, and stem cells of different origins, and is organized into secondary (and even tertiary) lymphoid organs, such as Peyer’s patches, cryptopatches, and isolated lymphoid follicles. The function of isolated lymphoid follicles is multifaceted; they play a role in the development and regeneration of the large intestine and the maintenance of (immune) homeostasis. Isolated lymphoid follicles are also extensively associated with the epithelium and its conventional and non-conventional immune cells; hence, they can also function as a starting point or maintainer of pathological processes such as inflammatory bowel diseases or colorectal carcinogenesis. These relationships can significantly affect both physiological and pathological processes of the intestines. We aim to provide an overview of the latest knowledge of isolated lymphoid follicles in colonic inflammation and colorectal carcinogenesis. Further studies of these lymphoid organs will likely lead to an extended understanding of how immune responses are initiated and controlled within the large intestine, along with the possibility of creating novel mucosal vaccinations and ways to treat inflammatory bowel disease or colorectal cancer.

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Moffett, J. R., K. L. Blinder, C. N. Venkateshan et M. A. A. Namboodiri. « Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs ». Cell & ; Tissue Research 293, n^o 3 (1998) : 525. http://dx.doi.org/10.1007/s004410051145.

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Maehara, Takashi, Hamid Mattoo, Vinay S. Mahajan, Samuel JH Murphy, Grace J. Yuen, Noriko Ishiguro, Miho Ohta et al. « The expansion in lymphoid organs of IL-4+ BATF+ T follicular helper cells is linked to IgG4 class switching in vivo ». Life Science Alliance 1, n^o 1 (janvier 2018) : e201800050. http://dx.doi.org/10.26508/lsa.201800050.

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Distinct T follicular helper (TFH) subsets that influence specific class-switching events are assumed to exist, but the accumulation of isotype-specific TFH subsets in secondary lymphoid organs (SLOs) and tertiary lymphoid organs has not been hitherto demonstrated. IL-4–expressing TFH cells are surprisingly sparse in human SLOs. In contrast, in IgG4-related disease (IgG4-RD), a disorder characterized by polarized Ig class switching, most TFH cells in tertiary and SLOs make IL-4. Human IL-4+ TFH cells do not express GATA-3 but express nuclear BATF, and the transcriptomes of IL-4–secreting TFH cells differ from both PD1hi TFH cells that do not secrete IL-4 and IL-4–secreting non-TFH cells. Unlike IgG4-RD, IL-4+ TFH cells are rarely found in tertiary lymphoid organs in Sjögren’s syndrome, a disorder in which IgG4 is not elevated. The proportion of CD4+IL-4+BATF+ T cells and CD4+IL-4+CXCR5+ T cells in IgG4-RD tissues correlates tightly with tissue IgG4 plasma cell numbers and plasma IgG4 levels in patients but not with the total plasma levels of other isotypes. These data describe a disease-related TFH subpopulation in human tertiary lymphoid organs and SLOs that is linked to IgG4 class switching.

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Camirand, Geoffrey, Fadi Lakkis et David Rothstein. « Maintenance and homeostatic proliferation of regulatory CD4 T cells occur independent of the thymus and of secondary lymphoid organs (104.7) ». Journal of Immunology 186, n^o 1_Supplement (1 avril 2011) : 104.7. http://dx.doi.org/10.4049/jimmunol.186.supp.104.7.

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Abstract In vivo manipulations that influence regulatory Foxp3+CD4+ T cells (Treg) homeostasis represent a valuable therapeutic mean for balancing immunity and regulation. However, the signals and the anatomical sites of Treg homeostasis are not completely defined. Therefore, we investigated the role of the thymus, and of secondary lymphoid organs (SLO) on Treg homeostasis in steady state. The absolute numbers of conventional CD4 T cells (Tconv) and Treg in spleen, peripheral lymph nodes, bone marrow, blood, liver, and lungs were determined by flow cytometry in euthymic or thymectomized adult wt B6 mice and in mice lacking SLO (splenectomized Lymphotoxin receptor β knockout). Proliferation was measured by EdU incorporation over a period of 3 days prior to analysis. We found that, in wt B6 mice, Treg exhibited a much higher rate of homeostatic proliferation (HP) than Tconv in both lymphoid and non-lymphoid compartments. Thymectomy of adult B6 mice reduced Tconv numbers in all compartments by 30-60%, while Treg numbers remained primarily unaffected (d30 and d60). In absence of SLO or both thymus and SLO, Treg accumulated in non-lymphoid organs, in blood, and in bone marrow in higher numbers and displayed similar rates of HP compared to wt mice. Our data show that Treg homeostasis occurs independently of thymic production and of SLO, suggesting an intrinsic Treg ability to respond to antigens in non-lymphoid tissues.

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Magrone, Thea, et Emilio Jirillo. « Development and Organization of the Secondary and Tertiary Lymphoid Organs : Influence of Microbial and Food Antigens ». Endocrine, Metabolic & ; Immune Disorders - Drug Targets 19, n^o 2 (7 février 2019) : 128–35. http://dx.doi.org/10.2174/1871530319666181128160411.

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Background:Secondary lymphoid organs (SLO) are distributed in many districts of the body and, especially, lymph nodes, spleen and gut-associated lymphoid tissue are the main cellular sites. On the other hand, tertiary lymphoid organs (TLO) are formed in response to inflammatory, infectious, autoimmune and neoplastic events. Developmental Studies: In the present review, emphasis will be placed on the developmental differences of SLO and TLO between small intestine and colon and on the role played by various chemokines and cell receptors. Undoubtedly, microbiota is indispensable for the formation of SLO and its absence leads to their poor formation, thus indicating its strict interaction with immune and non immune host cells. Furthermore, food antigens (for example, tryptophan derivatives, flavonoids and byphenils) bind the aryl hydrocarbon receptor on innate lymphoid cells (ILCs), thus promoting the development of postnatal lymphoid tissues. Also retinoic acid, a metabolite of vitamin A, contributes to SLO development during embryogenesis. Vitamin A deficiency seems to account for reduction of ILCs and scarce formation of solitary lymphoid tissue. Translational Studies: The role of lymphoid organs with special reference to intestinal TLO in the course of experimental and human disease will also be discussed. Future Perspectives: Finally, a new methodology, the so-called “gut-in-a dish”, which has facilitated the in vitro interaction study between microbe and intestinal immune cells, will be described.

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Goto, Hiro, et Maria das Graças Prianti. « Immunoactivation and immunopathogeny during active visceral leishmaniasis ». Revista do Instituto de Medicina Tropical de São Paulo 51, n^o 5 (octobre 2009) : 241–46. http://dx.doi.org/10.1590/s0036-46652009000500002.

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Visceral leishmaniasis is caused by protozoan parasites of the Leishmania donovani complex. During active disease in humans, high levels of IFN-γ and TNF-α detected in blood serum, and high expression of IFN-γ mRNA in samples of the lymphoid organs suggest that the immune system is highly activated. However, studies using peripheral blood mononuclear cells have found immunosuppression specific to Leishmania antigens; this poor immune response probably results from Leishmania antigen-engaged lymphocytes being trapped in the lymphoid organs. To allow the parasites to multiply, deactivating cytokines IL-10 and TGF-β may be acting on macrophages as well as anti-Leishmania antibodies that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver and can be confirmed through the examination of organ samples. However, an analysis of sequential data from studies of visceral leishmaniasis in hamsters suggests that factors outside of the immune system are responsible for the early inactivation of inducible nitric oxide synthase, which occurs before the expression of deactivating cytokines. In active visceral leishmaniasis, the immune system actively participates in non-lymphoid organ lesioning. While current views only consider immunocomplex deposition, macrophages, T cells, cytokines, and immunoglobulins by diverse mechanism also play important roles in the pathogenesis.

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Caucheteux, Stephan M., Souheil A. Younes et William E. Paul. « CD45RB expression refines delineation of memory CD4 T cells and aids in understanding their development (91.8) ». Journal of Immunology 178, n^o 1_Supplement (1 avril 2007) : S161. http://dx.doi.org/10.4049/jimmunol.178.supp.91.8.

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Abstract Upon immunization, CD4 T cell stimulation leads to the development of effectors cells and of 2 major subsets of memory cells: central and effector memory cells, the latter often defined by their differential expression of CD62L and CD44. It is still unclear whether central memory cells derive from effectors or are directly induced. Our results have shown that CD44hi cells can be divided into 2 different subtypes depending on their expression level of CD45RB, providing a precise distinction among central and effector memory CD4 T cells. Using these markers, we show that while central memory CD4 T cells are absent in young mice, they are enriched in old and thymectomized animals To understand the properties of the subsets defined by CD45RB and the establishment of the central and effector memory pools, we followed the fate of transferred naïve 5C.C7 T cell receptor transgenic cells, specific for pigeon cytochrome. During the first days following immunization, virtually all the transferred cells adopt the phenotype associated with effector or effector memory cells. After a month, essentially all 5C.C7 cells in lymphoid organs express phenotypes associated with central memory cells, while in the lung effector T cells are still found. Analysis of the mean “life” of these memory cells and their cycling within the lymphoid and the non-lymphoid organs is under investigation. Taken together, these observations suggest that CD45RB, together with CD44 and CD62L, provides a powerful tool to identify and quantitate naïve, effector and memory cells in lymphoid and non-lymphoid organs. This work was supported by the Intramural Research Program of the NIAID.

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Tkachev, Victor, Scott N. Furlan, Benjamin K. Watkins, Angela Panoskaltsis-Mortari, Bruce R. Blazar et Leslie S. Kean. « Biological role of T Memory Stem Cells as a Cellular Reservoir for Graft-versus-Host Disease ». Journal of Immunology 196, n^o 1_Supplement (1 mai 2016) : 140.8. http://dx.doi.org/10.4049/jimmunol.196.supp.140.8.

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Abstract T memory stem cells (Tscm) are a subset of antigen-experienced, long-lived, self-renewing and multipotent T cells, which reconstitute immunity following hematopoietic cell transplantation (HCT). Here we investigated the biological role of Tscm in acute Graft-versus-Host Disease (GVHD) using a translational non-human primate model. Tscm cells were tracked longitudinally following autologous or allogeneic HCT under different immunoprophylaxis regimens, resulting either in fulminant Th1-dependent ‘Primary GVHD’, late-onset Th17-driven ‘Breakthrough GVHD’, or GVHD-free immune tolerance. Following HCT, Tscm acquired an activated phenotype (Ki67+, CD69+, PD-1+ and CCR5+), but produced low amounts of IFNγ, IL-2, IL-17A, TNFα and Granzyme B. Tscm were a minor population in donor grafts but expanded in peripheral blood (with a reciprocal decline of naïve T cells) early after HCT and then contracted (with a concomitant increase of effector T cells) when recipients developed clinical GVHD. The kinetics of Tscm expansion/contraction correlated closely with clinical disease: Tscm expanded slower and contracted later in animals progressing to Breakthrough compared to Primary GVHD, and Tscm numbers remained stable under tolerizing conditions. At necropsy, animals with GVHD had increased numbers of Tscm in both lymphoid organs (blood, lymph nodes, spleen) and non-lymphoid GVHD-target organs (colon, lungs, liver) compared to GVHD-free animals. Our data demonstrates that Tscm dynamics correlate with GVHD-free survival and suggest that pathogenic T cells infiltrating both lymphoid and non-lymphoid organs transition from the naïve into the effector state via Tscm. Thus Tscm may play a key role as a cellular reservoir for GVHD.

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Fotiadis, Constantine Iosif, I. Georgopoulos, C. Stoidis et P. Patapis. « Primary Tumors of the Spleen ». International Journal of Biomedical Science 5, n^o 2 (15 juin 2009) : 85–91. http://dx.doi.org/10.59566/ijbs.2009.5085.

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Tumors of the spleen are rare compared to the incidence of such tumors in other parenchymatous organs. Their classification has varied with both time and author. They can be divided into two main categories: nonlymphoid and lymphoid. The most common nonlymphoid tumors are the vascular tumors which include benign and malignant haemangiomas, littoral cell angiomas, lymphangiomas and haemangioendotheliomas. The remaining nonlymphoid tumors, such as fibrosarcoma, neurinoma, and lipoma are very uncommon. The lymphoid tumors include Hodgkin's and non Hodgkin's lymphoma, histiocytic lymphoma and plasmacytoma. Metastatic tumors to the spleen mainly originate from melanoma, breast and lung lesions. However, metastases to the spleen are rare compared to those of other parenchymatous organs.

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Smith, Corinne, Holly Turula et Christopher Snyder. « Systemic hematogenous maintenance of memory inflation by MCMV infection (VIR4P.1013) ». Journal of Immunology 192, n^o 1_Supplement (1 mai 2014) : 143.8. http://dx.doi.org/10.4049/jimmunol.192.supp.143.8.

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Abstract Cytomegalovirus (CMV) is a β-herpesvirus that establishes a latent infection and supports the life-long maintenance of very large numbers of virus-specific effector T cells. These T cells remain functional and are found in many organs in the body. Current models propose that, to sustain these populations, reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and differentiation, followed by migration of progeny to non-lymphoid tissues. We tested this model using murine CMV (MCMV). While MCMV transcriptional activity during latency was below our limit of detection, proliferation of MCMV-specific effector T cells was antigen-dependent and was used as a read-out for antigen encounter. As shown previously, T cells within draining lymph nodes divided at a higher rate than cells elsewhere. However, pulse-chase experiments with BrdU failed to reveal migration of recently divided T cells from lymphoid to non-lymphoid tissues. In fact, inflationary cells observed in non-lymphoid organs were primarily perfusion-resistant cells residing in the vasculature. Strikingly, inhibition of T cell egress from lymph nodes did not eliminate T cell division in circulation, and did not prevent the maintenance of the circulating inflationary population during long-term treatment. Together these results suggest that memory inflation in response to MCMV is driven by viral antigen presented by cells that are accessible to the blood supply.

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Borodin, Yu I., O. V. Gorchakova et V. N. Gorchakov. « PERIPHERAL LYMPHOID STRUCTURES : FORMATION AND FUNCTION ». Morphology 150, n^o 4 (15 août 2016) : 90–96. http://dx.doi.org/10.17816/morph.397757.

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The problem of the formation of new lymphoid structures (neolymphogenesis) is quite controversial and widely discussed in the literature. Under normal conditions, lymphoid organs arise only in the process of fetal development (organogenesis), however in long-standing chronic inflammatory processes, non-healing wounds, autoimmune diseases, oncologic pathology spontaneous formation of new lymphoid structures was noted. The structures of the peripheral lymphoid formations include the lymphocytes arranged singly and in clusters (infiltration), lymphoid nodules and lymph nodes. The morphogenesis of the components of lymphoid tissue and the possibility of creating artificial lymphoid structures, reproducing the function of the natural ones, is demonstrated. Important role in the development of lymphoid structures is played by mediators of inflammation, cytokines of the family of lymphotoxins, tumor necrosis factor. The possibilities of prosthetic substitution of the functions of the lymphoid structures are described for the activation of protective processes in the body.

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Chuluunbaatar, Tsolmon, Osamu Ichii, Md Abdul Masum, Takashi Namba et Yasuhiro Kon. « Morphological Characteristics of Genital Organ-Associated Lymphoid Tissue in the Vaginal Vestibule of Goats and Pigs ». Veterinary Sciences 10, n^o 1 (11 janvier 2023) : 51. http://dx.doi.org/10.3390/vetsci10010051.

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Mucosa-associated lymphoid tissue (MALT) is a specialized form of peripheral lymphoid tissue (LT), which is found on mucosal surfaces exposed to the environment. However, morphological data of these tissues in farm animals are scarce. This study investigated the gross anatomical and histological features of genital organ-associated lymphoid tissues (GOALTs) in the vaginal vestibule (VV) of healthy, non-pregnant, adult goats and pigs. Their VVs were composed of stratified squamous, non-keratinized epithelium, and various-sized dark-blue hematoxylin-positive spots were observed in whole-mount specimens, which were diffusely distributed throughout the mucosal surfaces. These spots were histologically identified as LTs and consisted of lymphatic nodules (LNs) or diffuse lymphoid tissue (DLTs). Both LNs and DLTs contained B cells, T cells, macrophages, dendritic cells, plasma cells, and high endothelial venules. Only the numbers of B cells were significantly higher in both the LNs and DLTs of pigs compared to goats. Furthermore, the surface of the VV epithelium covering the LTs was partially disrupted with a large intercellular space containing abundant connective tissue fibers with numerous lymphocytes. In conclusion, GOALTs in the VV appear to be common local immunological barriers in both examined animals. This knowledge is crucial for understanding the structures and disorders of female reproductive organs in farm animals.

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Somova, L. M., F. N. Shubin, E. I. Drobot, I. N. Lyapun et N. G. Plekhova. « Inflammation induced by different plasmid types of russian Yersinia pseudotuberculosis strains ». Russian Journal of Infection and Immunity 9, n^o 2 (12 juillet 2019) : 369–74. http://dx.doi.org/10.15789/2220-7619-2019-2-369-374.

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In the 2000s, a scientific interest to the Far Eastern scarlet-like fever (FESLF) mainly recorded In Russia and Japanwas remarkably increased. Such clinical and epidemic manifestation of human pseudotuberculosis is related to a certain bacterial clonal lineage characterized by a specific plasmid profile (pVM82, pYV48), sequence type (2ST) as well as the yadA gene allele (1st allele). In our study we examined features of inflammatory changes characterizing plasmidassociated pathogenicity of the FESLF pathogen. In addition, organ histopathology in experimental animals infected intraperitoneally with Y. pseudotuberculosis strains of the four plasmid types 48+:82+; 48+:82-; 48-:82+; 48-:82-; and 48-:82-was investigated. It was found that the mortality rate in animals infected with Y. pseudotuberculosis H-5015 strain (82+:48+) bearing two plasmids with a molecular weight of 82 and 48 MDa was 40%. A picture of diffuse pneumonia with moderate inflammatory infiltration in pulmonary tissue and changes in lymphoid organs characterizing immunodeficiency we observed as early as 3 days postinfection (p.i.). On the contrary, animals infected with Y. pseudotuberculosis H-5015 strain (82+:48–) bearing a single plasmid 82 MDa pVM, mortality rate was 30%. A vascular reaction in the lungs and liver as well as deteriorated vascular destructive changes were revealed starting from day 3 and on day 5–7 days p.i., respectively, which was paralleled with perivascular infiltration mainly by mononuclear cells and focal pneumonia as well as a reaction of bronchialassociated lymphoid tissue and minimal organ destructive changes. On day 7 p.i., signs of granulomatous inflammation in the liver in a form of small mononuclear cell clusters and perivascular compact infiltrates were found. At all time points, lymphoid organ hyperplasia was noted. In case the infection caused by H-5013 strain (48+), the mortality rate was 80%. Inflammatory changes with dominant mononuclear cells were detected as early as 1 day p.i. associated with a picture of large focal bronchopneumonia, more pronounced in the non-survivor animals, also demonstrating signs of severe immunosuppression in the lymphoid organs. Starting from day 3 p.i., lymphoid hypoplasia in the spleen and lymph nodes was detected in all infected animals paralleled with pathogen-associated tissue damage in various organs. Animals infected with the plasmid-free H-5013 strain 48-) resulted in 25% mortality rate. Moreover, starting from day 3 p.i., a slight mononuclear inflammatory infiltration in the lungs and liver, a moderate giant cell reaction in the splenic pulp, and loose perinodal inflammatory infiltration in the lymph nodes were observed. Thus, while modeling infection caused by different plasmid types of Y. pseudotuberculosis, the data on differences in histopathology of changes in diverse organs regarding dynamics and generalization of the inflammatory response, as well as the severity of pathogen-associated damage in the lymphoid tissue were obtained. In case Y. pseudotuberculosis strains contained pVM82 plasmid with or without virulence plasmid pYV vs. single pYV-positive strains, an area of the inflammatory response as well as severity of immunosuppression manifested by splenic and lymph node delymphatization were decreased. It allowed to suggest that pVM82 plasmid found In Russia-originatingY. pseudotuberculosisstrains might be implicated in limiting intensity of inflammatory response, bacterial dissemination and severity of lymphoid organ damage.

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Beilhack, Andreas, Stephan Schulz, Jeanette Baker, Georg F. Beilhack, Ryosei Nishimura, Gilad Landan, Enosh M. Baker, Edward I. Herman, Christopher H. Contag et Robert S. Negrin. « A Signal Hierarchy Model of Alloreactive T Cell Trafficking for the Organ Manifestation in Acute Graft-Versus-Host Disease. » Blood 108, n^o 11 (16 novembre 2006) : 72. http://dx.doi.org/10.1182/blood.v108.11.72.72.

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Abstract Acute graft-versus-host disease (aGVHD) is caused by alloreactive effector T cells attacking the gastrointestinal tract, liver and skin after allogeneic hematopoietic cell transplantation (aHCT). The mechanism by which alloreactive T cells target these organs and not others remains elusive. Recently, we reported that different secondary lymphoid organs (SLOs), as alloreactive priming sites, can imprint distinct homing phenotypes on evolving alloreactive effector cells in vivo. However, preventing access to selected lymphoid organs (via the use of blocking antibodies or recipient mice lacking Peyer’s patches (PP), PP and lymph nodes (LN) or spleens) did not alter the aGVHD organ manifestation. These findings not only suggested a high redundancy of SLOs as induction sites of aGVHD, but also questioned whether homing instruction of alloreactive T cells by these sites can explain the mechanism of aGVHD target organ manifestation. To test the homing instruction model we transplanted transgenic luciferase+ (luc+) FVB/N (H-2q, Thy1.1+) splenocytes into conditioned (2×400rad) Balb/c recipients (H-2d, Thy1.2+). On day+3 we isolated luc+ donor lymphocytes from peripheral LN, mesenteric LN, or spleens and transferred them into conditioned secondary allogeneic recipients. 16 hours later, bioluminescence imaging revealed that allogeneic luc+ T cells irrespective of their original priming site targeted the intestinal tract and liver. Subsequently, we compared aHCT of conditioned with non-conditioned secondary Balb/cRag−/− cγ-Chain−/− recipients. Surprisingly, we found allogeneic luc+ T cells accumulating in SLOs in non-conditioned recipients in contrast to intestinal and hepatic tissues in conditioned recipients. These in vivo findings establish that alloreactive effector cells migrate to aGVHD target tissues because of attraction to these sites rather than specific instruction by SLOs. Therefore, we propose a signal hierarchy model of alloreactive cell trafficking whereby inflammatory signal/ligand interactions dominate over organ-specific homing receptor/ligand interactions.

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Harahap, A. R., et J. W. Goding. « Distribution of the murine plasma cell antigen PC-1 in non-lymphoid tissues. » Journal of Immunology 141, n^o 7 (1 octobre 1988) : 2317–20. http://dx.doi.org/10.4049/jimmunol.141.7.2317.

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Abstract PC-1 is an alloantigen of murine plasma cells. Its close association with secretory function in lymphoid cells previously raised the question of whether PC-1 was part of the secretory apparatus. In addition to its expression on lymphocytes, PC-1 had been known to be present in liver, brain, and kidney, although the data were derived almost entirely from bulk absorption studies of polyclonal alloantisera, and virtually nothing was known about the nature of the cells expressing PC-1 in these organs. If PC-1 was functionally involved in the secretory process. it might be expected to be present at secretory sites within these and other organs. We now report the results of an immunohistochemical survey of the distribution of PC-1 in a variety of non-lymphoid organs, using a mAb. The PC-1 Ag was found in a small number of highly discrete locations that were mostly, but not exclusively, associated with epithelia. Sites of strong expression included the distal convoluted tubule of the kidney, ducts of the salivary glands, epididymis, proximal part of the vas deferens, and chondrocytes. The PC-1 glycoprotein was also found in the capillaries of the brain, but did not appear to be present in capillaries elsewhere, a pattern that is strikingly similar to that of the receptor for the iron transport protein, transferrin. Negative sites included the thyroid, pancreas, choroid plexus, smooth and striated muscle, stomach, small and large intestine, gall bladder, renal glomeruli, testis, and seminal vesicles. These results are not consistent with a generalized role for PC-1 in secretion, but are compatible with a role in a specialized subset of macromolecular transport events.

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Hughes, Derralynn A., Iain P. Fraser et Siamon Gordon. « Murine macrophage scavenger receptor:in vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs ». European Journal of Immunology 25, n^o 2 (février 1995) : 466–73. http://dx.doi.org/10.1002/eji.1830250224.

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Siemionow, Maria, Lucile Chambily et Sonia Brodowska. « Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model ». Biomedicines 12, n^o 5 (11 mai 2024) : 1064. http://dx.doi.org/10.3390/biomedicines12051064.

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Cell-based therapies hold promise for novel therapeutic strategies in regenerative medicine. We previously characterized in vitro human umbilical di-chimeric cells (HUDCs) created via the ex vivo fusion of human umbilical cord blood (UCB) cells derived from two unrelated donors. In this in vivo study, we assessed HUDC safety and biodistribution in the NOD SCID mouse model at 90 days following the systemic intraosseous administration of HUDCs. Twelve NOD SCID mice (n = 6/group) received intraosseous injection of donor UCB cells (3.0 × 106) in Group 1, or HUDCs (3.0 × 106) in Group 2, without immunosuppression. Flow cytometry assessed hematopoietic cell surface markers in peripheral blood and the presence of HLA-ABC class I antigens in lymphoid and non-lymphoid organs. HUDC safety was assessed by weekly evaluations, magnetic resonance imaging (MRI), and at autopsy for tumorigenicity. At 90 days after intraosseous cell administration, the comparable expression of HLA-ABC class I antigens in selected organs was found in UCB control and HUDC therapy groups. MRI and autopsy confirmed safety by no signs of tumor growth. This study confirmed HUDC biodistribution to selected lymphoid organs following intraosseous administration, without immunosuppression. These data introduce HUDCs as a novel promising approach for immunomodulation in transplantation.

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Han, Qian, Dandan Dong, Xiaojuan Zhang, Cuicui Liang, Qiongxuan Lu et Huarong Guo. « Problems with the use of liposome- and retrovirus-mediated gene transfer methods in the primary lymphoid cells of the Oka organs of the greasyback shrimp, Metapenaeus ensis (De Haan, 1844) ». Crustaceana 88, n^o 12-14 (2015) : 1351–65. http://dx.doi.org/10.1163/15685403-00003498.

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In this study, both liposome- and retrovirus-mediated gene transfer methods were examined for their potential to transfer and express two retroviral vectors containing the mouse c-Myc or the green fluorescent protein (GFP) gene into the primary lymphoid cell cultures (OKA) derived from “Oka” organs (= organs of the lymphoid system) of the greasyback shrimp Metapenaeus ensis (De Haan, 1844). It was found that the c-Myc gene could be delivered into OKA cells by the liposome-mediated method, but the introduced c-Myc gene could not be effectively transcribed into mRNA. In contrast, the pantropic retrovirus-mediated method failed to introduce the c-Myc gene into OKA cells, and GFP was not detected in the transformed cells, either. This work inferred two problems for the use of the two above-mentioned gene transfer methods in the non-dividing OKA cells: (1) the viral promoter of long terminal repeats (LTRs) had low activity in shrimp cells; (2) the pantropic retrovirus-mediated gene transfer system had a low tropism to shrimp lymphoid cells.

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Zhou, Yifan, Rachel L. Babcock, Taylor T. Chrisikos, Bhakti Patel, Yusra B. Medik, Laura M. Kahn, Haiyan S. Li et Stephanie S. Watowich. « Roles for STAT5 in homeostasis and function of CD103+cDC1s in non-lymphoid organs ». Journal of Immunology 206, n^o 1_Supplement (1 mai 2021) : 93.06. http://dx.doi.org/10.4049/jimmunol.206.supp.93.06.

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Abstract Type 1 conventional dendritic cells (cDC1s) have critical roles in inducing adaptive immune responses and mediating immune tolerance. Signal Transducer and Activator of Transcription 5 (STAT5) was found to be crucial for monocyte-derived DC development; however, its role in non-lymphoid tissue CD103+cDC1s remained largely unknown. We evaluated the role of STAT5 by employing myeloid-specific Stat5-deficient mice,LysM-Cre +Stat5f/f and CD11c-Cre+Stat5f/f mice. Both strains show deficiencies in the numbers of CD103+cDC1s and alveolar macrophages (AMs) in lung, suggesting ineffective maintenance of lung homeostasis. Consistent with this concept, CD11c-Cre+Stat5f/f mice show granulocyte and monocyte accumulation in lung, accompanied by a reduction in the number of CD4+T, CD8+T, and B cells. Moreover, CD11c-Cre+Stat5-deficient mice have increased numbers of alveolar histiocytes, which are also enlarged, as well as accumulation of amorphous and eosinophilic material in alveolar spaces, alveolar histiocytosis, and proteinosis. In addition to the lung, liver CD103+cDC1s were also decreased by Stat5 depletion, however colon CD103+cDC1s were not affected. To examine cell-autonomous roles for STAT5, we generated Stat5-deficient CD103+cDC1s using our established bone marrow culture system, and tested in vitro-differentiated CD103+cDC1s for antigen presentation activity. These assays suggest Stat5 deficiency impaired CD103+cDC1s antigen cross-presentation ability. Taken together, our study showed that STAT5 is required for homeostasis and function of CD103+cDC1s in non-lymphoid organs.

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Durant, S., D. Duval et F. Homo-Delarche. « Effect of cortisol on the plasma and lymphoid tissue distributions of tritiated glucocorticoids in C57BL/6 mice ». Journal of Endocrinology 117, n^o 3 (juin 1988) : 373–78. http://dx.doi.org/10.1677/joe.0.1170373.

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ABSTRACT The mechanism of action of very high doses of corticosteroids, such as those administered as bolus doses in the treatment of inflammatory and immune diseases or those currently used in rodents to isolate the small proportion of medullary thymocytes considered to be corticoresistant, is still undefined. The possible existence of selective local concentration by some tissues, particularly lymphoid organs, cannot be excluded. Therefore, using C57BL/6 mice, the kinetics of lymphoid tissue and plasma radioactivities after i.p. injection of steroids, either alone or with an excess of non-radioactive cortisol hemisuccinate (up to 10 mg/animal, i.e. 500 mg/kg ) were studied. There was a rapid and dose-dependent retention of [3H]corticosterone and [3H]cortisol in the thymuses of cortisol-treated compared with control animals. The spleen also appeared to be capable of accumulating steroids. However, when the tissue/plasma ratio of [3H]steroid concentration and the change in extracellular space in the presence of an excess of non-radioactive cortisol were taken into consideration, only the thymus was able to concentrate steroids above concentrations in the plasma. Moreover, this effect did not appear to be specific for glucocorticoids, since tracer accumulation was also observed when sex steroids were used as tracers. The cells of the reticuloendothelial system may, in part, be responsible for this phenomenon of steroid concentration in lymphoid organs. J. Endocr. (1988) 117, 373–378

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Gerner, Michael Y., Weizhe Li et Ronald N. Germain. « Novel tissue clearing method for preservation of morphology, fluorescence and epitope integrity permits quantitative cellular analysis in intact organs ». Journal of Immunology 196, n^o 1_Supplement (1 mai 2016) : 69.8. http://dx.doi.org/10.4049/jimmunol.196.supp.69.8.

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Abstract Spatial organization of cells within tissues is critical for most biological processes, such as cellular differentiation, signal relay, and localized function. Our understanding of such events is historically based on section imaging, which discards 3-dimensional (3D) information and is problematic for understanding structure-function relationships of complex tissues and rare events. Although recent innovations in tissue clearing methods have paved way for whole organ microscopy, they suffer from various technique-specific artifacts, such as fluorophore quenching, poor epitope preservation, or morphological distortions. Here we report a new clearing method, Clearing-enhanced 3D (Ce3D), which generates excellent tissue transparency, preserves cellular morphology and protein fluorescence, and retains epitopes for antibody-based labeling. We use Ce3D to demonstrate whole-tissue microscopy of various cell types in lymphoid and non-lymphoid organs. Further, when coupled with highly multiplexed antibody labeling and Histo-Cytometry, Ce3D permits quantitative analysis of phenotypically complex cells in intact tissues. Collectively, this methodology provides a comprehensive strategy for whole-organ quantitative imaging and analysis, paving the way for improved understanding of cellular organization and physiology. This research was supported by the Intramural Research Program of the NIH, NIAID.

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Pabst, Reinhard, et Richard M. Binns. « Heterogeneity of Lymphocyte Homing Physiology : Several Mechanisms Operate in the Control of Migration to Lymphoid and Non-Lymphoid Organs In Vivo ». Immunological Reviews 108, n^o 1 (avril 1989) : 83–109. http://dx.doi.org/10.1111/j.1600-065x.1989.tb00014.x.

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Huang, Xinglan, Peng Yan, Xinghua Song, Suiying Zhang, Yuqiong Deng, Caifeng Huang, Xiaoqing Zhao, Sheng Liu, Xiping Cheng et Dongjiang Liao. « MT-CO1 expression in nine organs and tissues of different-aged MRL/lpr mice : Investigation of mitochondrial respiratory chain dysfunction at organ level in systemic lupus erythematosus pathogenesis ». Archives of Rheumatology 37, n^o 4 (29 juillet 2022) : 504–16. http://dx.doi.org/10.46497/archrheumatol.2022.9168.

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Objectives: This study aims to investigate the expression patterns of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) in different organs and tissues of MRL/lpr mice aged six and 18 weeks. Materials and methods: Six-week-old female MRL/lpr mice (n=10) were considered young lupus model mice, and 18-week-old MRL/lpr mice (n=10) were considered old lupus model mice. Additionally, six-week-old (n=10) and 39-week-old (n=10) female Balb/c mice were used as the young and old controls, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of MT-CO1 in nine organs/tissues were detected via quantitative polymerase chain reaction (qPCR) and Western blot. Malondialdehyde (MDA) levels were determined with thiobarbituric acid colorimetry. The correlation coefficient of MT-CO1 mRNA levels and MDA levels in each organ/tissue at different ages was analyzed by Pearson correlation analysis. Results: The results showed that most non-immune organs/tissues (heart, lung, liver, kidneys, and intestines) showed increased MT-CO1 expression levels in younger MRL/lpr mice (p<0.05) and decreased MT-CO1 expression in older mice (p<0.05). Expression of MT-CO1 in the lymph nodes was low in younger mice but high in older mice. In other immune organs (spleen and thymus), MT-CO1 expression was low in older MRL/lpr mice. Lower mRNA expression and higher MDA levels were observed in the brains of MRL/lpr mice. However, all MRL/lpr mice showed higher MDA levels than Balb/c mice in every organ no matter younger or older MRL/lpr mice. Conclusion: Our study results suggest that lymphoid mitochondrial hyperfunction at organ level may be an important intrinsic pathogenesis in systemic lupus erythematosus activity, which may affect mitochondrial dysfunction in non-immune organs.

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Eken, Ahmet, Rebekka Duhen, Akhilesh K. Singh, Mallory Fry, Jane H. Buckner, Mariko Kita, Estelle Bettelli et Mohamed Oukka. « S1P1 deletion differentially affects TH17 and Regulatory T cells ». Journal of Immunology 196, n^o 1_Supplement (1 mai 2016) : 186.5. http://dx.doi.org/10.4049/jimmunol.196.supp.186.5.

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Abstract Sphingosine-1 phosphate receptor 1 (S1P1) is a G-protein coupled receptor critical for the egress of T and B cells out of lymphoid organs. Although S1P1 agonists (such as fingolimod) are currently used for the treatment of multiple sclerosis (MS) little is known how S1P1 signaling regulates Th17 and Treg cell homeostasis. To study the impact of S1P1 signaling on Th17 and Treg biology, we specifically deleted S1P1 in Th17 and Treg cells using IL-17ACre and Foxp3Cremice, respectively. Deletion of S1P1 in Th17 cells conferred resistance to experimental autoimmune encephalomyelitis (EAE) characterized by reduced Th17 cell distribution across peripheral organs and diminished Th17 cell generation. On the other hand, permanent deletion of S1P1 in Treg cells resulted in autoimmunity and acute deletion rendered mice more susceptible to EAE. Importantly, our study revealed that S1P1 not only regulated the egress of Treg cells out of lymphoid organs and subsequent non-lymphoid tissue distribution but also their phenotypic diversity. Most of the Treg cells found in S1P1-deficient mice had an activated phenotype and were more prone to apoptosis, thus converted to effector Treg. The comparison of Treg cells obtained from MS patients treated with fingolimod to those treated with other oral drugs confirmed the switch of Treg cells into effector memory phenotype. Our results provide novel insight into the functions of S1P1 and potential impact of long term fingolimod use on Th17 and Treg cell biology and general health in MS patients.

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Kapoor, Varun, et Raymond Welsh. « IL-2 regulates tissue-dependent differences in CD8 T cell apoptosis during and after- viral Infection. (110.19) ». Journal of Immunology 188, n^o 1_Supplement (1 mai 2012) : 110.19. http://dx.doi.org/10.4049/jimmunol.188.supp.110.19.

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Abstract Virus-specific CD8 T cell populations in lymphoid organs contract by apoptosis or by dissemination into peripheral tissues, and those residing in non-lymphoid organs, including the peritoneal cavity (PEC: peritoneal exudate cells), are more resistant to apoptosis than those in the lymphoid organs, including the spleen. We questioned whether tissue-dependent apoptotic differences in LCMV-specific T cells were due to environment factors or intrinsic stability of the CD8 T cells. The PEC environment conferred an anti-apoptotic effect, as shown by mixing PEC with excess splenic leukocytes or vice versa. This anti-apoptotic effect correlated with Stat5 phosphorylation induced by IL-2 spontaneously secreted by CD4 T cells. Spontaneous IL-2 production by CD4 T cells occurred in vivo during the contraction and the long term memory stage after LCMV infection in PEC and Fat pads, but much less so in spleen and lymph nodes. Virus-specific CD8 T cells in the PEC were also intrinsically more stable, as most had a memory precursor effector cell (MPEC) phenotype and higher expression of CD27, both correlating with decreased apoptosis. However, regardless of their phenotype, PEC CD8 T cells remained less apoptotic than their spleen cell counterparts. We conclude that long after the resolution of viral infections, IL-2-producing CD4 T cells linger in peripheral sites and locally contribute to the stability of memory CD8 T cells, thereby enhancing resistance to re-infection.

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Sizova, Olga, Denis Kuriatnikov et Dong-Ming Su. « Atrophied thymus can serve as a tumor reservoir for harboring melanoma cells ». Journal of Immunology 200, n^o 1_Supplement (1 mai 2018) : 178.2. http://dx.doi.org/10.4049/jimmunol.200.supp.178.2.

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Abstract Tumor metastatic relapse is responsible for main cancer associated mortality and potentially arises from undetectable minimal number of tumor cells, which are able to resist radio-chemotherapy at a dormant state hiding in certain organs (termed: tumor reservoirs). A central T cell immune organ, the thymus, has been suggested as this kind of pre-metastatic tumor reservoir for B-lymphoma cells, which are a risk for eventual relapse. It remains unknown whether the thymus is able to harbor non-lymphoid solid tumor cells, why chemotherapy cannot thoroughly eliminate cancer cells in the thymus, and what the state of thymic occult cancer cells is during chemotherapy. With melanoma inoculated and genotoxic doxorubicin treated mouse model, we determined that the thymus, particularly the atrophied thymus, was able to harbor blood stream-circulating melanoma cells. We found that chemotherapy-resulted DNA-damage response triggered p53 activation in non-malignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic occult minimal tumor cells to acquire heterogenic chemo-resistant dormancy. Therefore, the thymus, which becomes a pre-metastatic reservoir for non-lymphoid solid tumor cells under chemotherapy, should be a novel target in antitumor therapy for considering and preventing from tumor metastatic relapse.

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Mercy Paul M et Sukumar Naidu KD. « A case report on BPDCN : Blastic Plasmacytoid Dendritic Cell Neoplasm ». World Journal of Advanced Research and Reviews 19, n^o 2 (30 août 2023) : 091–98. http://dx.doi.org/10.30574/wjarr.2023.19.2.1469.

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Dendritic cells are present in both lymphoid and non-lymphoid organs, which are heterogenous group of nonphagocytic and nonlymphoid immune accessory cells. Plasmacytoid dendritic cell (which has an eccentric nuclei) are subset of dendritic cells aid in secreting high levels of type 1 interferons by activation and gaining dendritic cell like morphology, play an important role in antiviral immunity and are involved in initiation and development stages of inflammatory response. The initial presentation of extra-cutaneous region is an involvement of regional lymph nodes later progressed to bone marrow and peripheral blood. When bone marrow is extensively involved, neoplastic cells interfere peripheral blood resembling as circulating leukemic myeloid or lymphoid blasts. BPDCN is confused with cutaneous peripheral T-cell lymphoma due to cutaneous involvement. Comparative to adults, BPDCN in children are less aggressive. Intensive 1st line therapy along with “Lymphoid type” chemotherapy show better results. Lymphodenopathy, splenomegaly, bone marrow involvement and cytopenia, cutaneous lesions are observed widely.

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Won, Haejung, Yuchia Chou, Tao Wang, Lindsey Jones, Xue Huang et Si-Yi Chen. « Histone H2A deubiquitinase MYSM1 is essential for dendritic cell development (P4488) ». Journal of Immunology 190, n^o 1_Supplement (1 mai 2013) : 52.61. http://dx.doi.org/10.4049/jimmunol.190.supp.52.61.

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Abstract The mechanisms controlling differentiation of dendritic cells remain largely unknown. Using knockout mouse model, we identified Mysm1 as a critical regulator in dendritic cell differentiation. Mysm1 knockout mice showed a global reduction of both conventional dendritic cells and plasmacytoid dendritic cells in lymphoid organs and non-lymphoid organs whereas development of granulocyte and macrophage was not severely affected. Hematopoietic progenitors and dendritic cell precursors were significantly decreased in KO mice, and the precursor cells from Mysm1 knockout mice were unable to develop DC upon Flt3L stimulation in vitro. The developmental defect of Mysm1-/- progenitor cells was associated with decreased Flt3 expression. Molecular studies indicate that Mysm1 de-represses transcription of Flt3 gene by regulating histone modifications and mediating the recruitment of transcription factor Pu.1 at the promoter. In conclusion, we have identified a regulator of dendritic cell development, Mysm1, and provided novel mechanism of epigenetic control in steady-state dendritic cell development.

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Matsuura, Y., T. Matsuoka et Y. Fuse. « Ultrastructural and immunohistochemical studies on the ontogenic development of bronchus-associated lymphoid tissue (BALT) in the rat : special reference to follicular dendritic cells ». European Respiratory Journal 5, n^o 7 (1 juillet 1992) : 824–28. http://dx.doi.org/10.1183/09031936.93.05070824.

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The ontogenic development of lymphoid and non-lymphoid cells in bronchus-associated lymphoid tissue (BALT) of the rat was studied ultrastructurally and immunohistochemically. In the late foetal period, only the alveolar macrophages showed a weak positivity for leucocyte common antigen, but no immune region associated (Ia) antigen was detected by monoclonal antibody, MAS 043. Mast cells were present. At 6 days of age, Ia-positive cells were observed in the alveolar wall and peribronchial interstitial tissue, and ultrastructurally there was an aggregation of the fibroblastoid mesenchymal cells. By 10 days of age, the aggregation of lymphoid cells together with S-100-positive reticulum cells had formed a BALT-like periarterial lymphoid sheath. In the adult animals, an obvious B-cell area was present in the central part and subepithelium of BALT, whilst in this area, S-100-positive, strongly Ia-positive cells with a dendritic form were observed. These dendritic cells appeared to be identical to the follicular dendritic cells (FDC) seen in the secondary follicles of lymphoid organs. Those cells may be derived from the fibroblastic reticulum cells, and may function to present antigen to lymphocytes.

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Isham, Ishara M., Mohamed S. H. Hassan, Reham M. Abd-Elsalam, Hiruni A. Ranaweera, Motamed E. Mahmoud, Shahnas M. Najimudeen, Awais Ghaffar, Susan C. Cork, Ashish Gupta et Mohamed Faizal Abdul-Careem. « Impact of Maternal Antibodies on Infectious Bronchitis Virus (IBV) Infection in Primary and Secondary Lymphoid Organs of Chickens ». Vaccines 11, n^o 7 (7 juillet 2023) : 1216. http://dx.doi.org/10.3390/vaccines11071216.

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Infectious bronchitis virus (IBV) causes infectious bronchitis disease in chickens. IBV primarily infects the upper respiratory tract and then disseminates to other body systems including gastrointestinal, reproductive, and urinary systems. Unlike original IBV serotypes, the novel IBV variants target lymphoid organs, but information on this is scarce. In this study, we aim to evaluate the impact of the presence of maternal antibodies on IBV infection in primary and secondary lymphoid organs. Maternal antibody free, specific pathogen free (SPF) hens were divided into vaccinated and non-vaccinated groups. The progeny male chicks from these hens were divided into four groups; vaccinated challenged (VC), non-vaccinated challenged (NVC), vaccinated non-challenged (VNC), and non-vaccinated non-challenged (NVNC). The challenge groups were given 1 × 106 embryo infectious dose (EID)50 of IBV Delmarva (DMV)/1639 by the oculo-nasal route and non-challenge groups were given saline. The serum anti-IBV antibody titer was significantly higher in challenged groups compared to non-challenged groups. The IBV genome load was significantly lower in the VC group than NVC group in oropharyngeal and cloacal swabs and in bursa of Fabricius (BF) and cecal tonsils (CT). The histopathological lesion scores were significantly lower in VC group than NVC group in BF and CT. These findings suggest that the presence of maternal antibody in chicks could provide some degree of protection against IBV infection in BF and CT.

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Omatsu, Tsutomu, Meng Ling Moi, Takanori Hirayama, Tomohiko Takasaki, Shinichiro Nakamura, Shigeru Tajima, Mikako Ito et al. « Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection : development of high levels of viraemia and demonstration of protective immunity ». Journal of General Virology 92, n^o 10 (1 octobre 2011) : 2272–80. http://dx.doi.org/10.1099/vir.0.031229-0.

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Dengue virus (DENV) causes a wide range of illnesses in humans: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Animal models that constantly develop high levels of viraemia are required for the development of protective and preventive measures. Common marmosets (Callithrix jacchus) demonstrated high levels of viraemia after inoculation with clinical isolates of four serotypes of DENV; in particular, over 106 genome copies ml−1 after inoculation with DENV-2. Non-structural protein 1 and DENV-specific IgM and IgG antibodies were consistently detected. The DENV-2 genome was detected in lymphoid organs including the lymph nodes, spleen and thymus, and also in non-lymphoid organs. DENV antigen was detected by immunohistochemistry in the liver and spleen from inoculated marmosets. Four marmosets were reinoculated with DENV-2 at 33 weeks after primary inoculation with DENV-2. The DENV-2 genome was not detected in any of these marmosets, indicating protection from a secondary infection. The results indicate that common marmosets are highly sensitive to DENV infection, and suggest that marmosets could be a reliable primate model for the evaluation of candidate vaccines.

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Mykhailiutenko, S. M., O. V. Kruchynenko, J. K. Serdioucov, O. S. Klymenko et J. D. Popovytch. « Pathomorphological changes in parenchymatose organs of rabbits in case of chronic passalurosis ». Scientific Messenger of LNU of Veterinary Medicine and Biotechnology 21, n^o 93 (2 avril 2019) : 31–36. http://dx.doi.org/10.32718/nvlvet9306.

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Pathomorphological changes, developing in case of pasalurosis chronic course in rabbits are described in the article. The research was held on ten rabbits of Large Grey breed, which were held on household farms of Poltava region. The diagnosing was complex: based on anamnesis data, clinical symptoms’ analysis, and the results of pathomorphological examination. The fragments of the liver, spleen, and kidneys were taken for histological analysis. While making histological analysis of the spleen it was revealed that lymphoid nodules were enlarged, some of them were of uniform structure, and others were in the state of hyperplasia. Non-uniformity of structure in addition to changing the size was registered in those nodules: there was less concentration of lymphoid cells in their central part and more concentration on the periphery. The situation was contrary in separate lymphoid nodules. The red pulp consisted of a large number of lymphoid cells and erythrocytes, the largest number of which were registered in the zones adjoining the places of lymphoid nodules’ location. Sometimes there were megakaryocytes in the field of vision. It was established, that blood filling of arteries was less than normal. In case of using some preparations, bilirubin inclusions were found at having big enlargements in red pulp. Grainy and fatty hepatocytes’ dystrophies, and also lymphohistiocytic interstitial hepatitis were also registered. At the same time, renal corpuscles were enlarged. Rather big spaces, filled with transparent substance containing vessel and cellular fragments (detritus), were revealed in the majority of them between glomeruli and the capsule.Capsule epithelial cells were destroyed in some places. Petechial hemorrhages were registered inside glomeruli. The destruction of separate podocytes and deep cells was noticed. The tubular epithelial cells were enlarged in size, and in some cases they were of cylinder, but not cubic shape; the spaces of such tubular were becoming correspondingly less. The epithelial cell cytoplasm of the tubular in some cases was not uniformand it was of cloudy-grey color: in other cases it had rather large colorless areas and, probably, looked like lipid inclusions (which were washed out from the cells as a result solvent impact during making histological preparations). Concentrations of eosinophilic masses (protein cylinders) sometimes containing certain amount of erythrocytes were often found in canaliculi spaces. Sometimes the destruction of epithelial cells was registered in the tubulеs, and their fragments were found in spaces. As a result of histological examination, the diffuse lymphohistiocytic infiltration in the renal interstitial tissue was found.

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Maggi, E., P. Parronchi, D. Macchia, G. Bellesi et S. Romagnani. « High numbers of CD4+ T cells showing abnormal recognition of DR antigens in lymphoid organs involved by Hodgkin's disease ». Blood 71, n^o 5 (1 mai 1988) : 1503–6. http://dx.doi.org/10.1182/blood.v71.5.1503.1503.

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Abstract Purified T lymphocytes (E rosetting cells) isolated from the involved lymphoid organs (lymph nodes and spleen) of five patients with Hodgkin's disease (HD) were cloned under culture conditions (phytohemagglutinin plus interleukin-2) that allow clonal expansion of most T lymphocytes. A total number of 104 CD4+ T cell clones so obtained were tested for their ability to proliferate in response to autologous mitomycin-treated non-T cells. About half of these clones but none of 234 CD4+ T cell clones derived from normal lymphoid tissues or peripheral blood displayed a proliferative response to autologous stimulators. When clones proliferating in autologous mixed lymphocyte reaction (AMLR) were assessed for their ability to respond in allogeneic MLR (allo-MLR), most of them were found to exhibit consistent proliferation in response to more than one haplotype. Both the AMLR and the allo-MLR by HD clones were inhibited by adding monoclonal antibodies (MoAbs) reactive with monomorphic determinants of major histocompatibility complex (MHC) class II (DR) antigens to the cultures, whereas MoAbs reactive with MHC class I antigens were without effect. These studies suggest that lymphoid organs involved by HD contain high proportions of CD4 T cells showing abnormal recognition of DR antigens. These unusual cells may play an important role in the pathogenetic mechanisms occurring in HD.

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Maggi, E., P. Parronchi, D. Macchia, G. Bellesi et S. Romagnani. « High numbers of CD4+ T cells showing abnormal recognition of DR antigens in lymphoid organs involved by Hodgkin's disease ». Blood 71, n^o 5 (1 mai 1988) : 1503–6. http://dx.doi.org/10.1182/blood.v71.5.1503.bloodjournal7151503.

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Purified T lymphocytes (E rosetting cells) isolated from the involved lymphoid organs (lymph nodes and spleen) of five patients with Hodgkin's disease (HD) were cloned under culture conditions (phytohemagglutinin plus interleukin-2) that allow clonal expansion of most T lymphocytes. A total number of 104 CD4+ T cell clones so obtained were tested for their ability to proliferate in response to autologous mitomycin-treated non-T cells. About half of these clones but none of 234 CD4+ T cell clones derived from normal lymphoid tissues or peripheral blood displayed a proliferative response to autologous stimulators. When clones proliferating in autologous mixed lymphocyte reaction (AMLR) were assessed for their ability to respond in allogeneic MLR (allo-MLR), most of them were found to exhibit consistent proliferation in response to more than one haplotype. Both the AMLR and the allo-MLR by HD clones were inhibited by adding monoclonal antibodies (MoAbs) reactive with monomorphic determinants of major histocompatibility complex (MHC) class II (DR) antigens to the cultures, whereas MoAbs reactive with MHC class I antigens were without effect. These studies suggest that lymphoid organs involved by HD contain high proportions of CD4 T cells showing abnormal recognition of DR antigens. These unusual cells may play an important role in the pathogenetic mechanisms occurring in HD.

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46

Elmeligy, Abdelmenem, Ali Ghania et Ahmed Fotouh. « Pathological and immunohistochemical studies of lymphoid leukosis in pigeons in Egypt ». Open Veterinary Journal 14, n^o 8 (2024) : 1952. http://dx.doi.org/10.5455/ovj.2024.v14.i8.24.

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Background: Pigeon leukosis is primarily caused by avian leukosis virus subgroup A (ALV-A). It infects and transforms lymphoid cells, leading to the development of tumors in various lymphoid tissues and other organs especially the liver. Aim: This study was conducted to diagnose lymphoid leukosis in a naturally infected pigeon flock in Egypt. Methods: Tissue specimens from the liver, spleen, thymus, kidney, lung, proventriculus, gizzard, intestine, pancreas, heart, pectoral muscle, ovary, and testes were collected from infected birds for pathological and immunohistochemical examinations. Results: Clinical signs were generally non-specific and comprised weakness, dehydration, and emaciation. Gross lesions were mostly in the liver and spleen, in the form of minute white nodules scattered on the liver surface. Microscopic examination of the liver, spleen, and kidneys showed masses of uniform sizes and the presence of differentiated lymphoid cells. These cells appeared as large mononuclear cells with poorly defined cell membranes. Immunohistochemical investigation exhibited that the ALV-A positive indicators were chiefly accessible in the liver, ovary, spleen, and kidney. Conclusion: Lymphoid leukosis in pigeons could be provisionally diagnosed by a pathological picture of characteristic tumors and confirmed by immunoreactivity of viral antigens in different tissues.

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Maillard, Ivan. « From Graft-Versus-Host Disease to Lymphoma Pathogenesis : Emerging Roles for Stromal Notch Ligands in Hematology ». Blood 134, Supplement_1 (13 novembre 2019) : SCI—47—SCI—47. http://dx.doi.org/10.1182/blood-2019-121067.

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Notch signaling is a highly conserved signaling pathway with multiple functions in health and disease. Notch ligands of the Delta-like and Jagged families interact with Notch1-4 on adjacent cells to trigger proteolytic activation of the Notch receptors, followed by context-dependent transcriptional activation of Notch target genes. In the hematopoietic system, Notch was first identified for its oncogenic role in T cell acute lymphoblastic leukemia (T-ALL). More recently, Notch has been recognized as a recurrent oncogenic pathway in multiple B cell lymphoproliferative disorders, including CLL/SLL, mantle cell lymphoma and marginal zone lymphoma. In parallel, essential functions of Notch signaling have been identified in early T cell development and B cell homeostasis, as well as in regulating T and B cell immune responses in secondary lymphoid organs. We have discovered a conserved pathogenic function of Notch signaling in the control of graft-versus-host disease (GVHD), both in mouse and non-human primate models of hematopoietic cell transplantation. Within days after allogeneic hematopoietic cell transplantation, donor-derived T cells interact with Delta-like Notch ligands expressed by specialized subsets of non-hematopoietic fibroblastic stromal cells in spleen and lymph nodes. In turn, Notch signaling programs alloreactive T cells to become pathogenic effector cells that mediate long-term damage in GVHD target tissues, while suppressing the expansion of regulatory T cells. Emerging evidence suggests the existence of an active crosstalk between T cells, B cells and well-defined specialized immunological stromal niches expressing Notch ligands in secondary lymphoid organs, both in GVHD and in other types of immune responses. Moreover, many B cell lymphomas demonstrate oncogenic Notch activation as a result of gain-of-function mutations that increase the persistence of intracellular Notch after proteolytic cleavage, thus requiring the presence of Notch ligands in the microenvironment to trigger oncogenic Notch signals. New evidence suggests that key Notch ligands in human lymphomas are present in the lymph node microenvironment, and that oncogenic Notch activation can happen even in the absence of mutations in a substantial fraction of lymphoma patients, including the majority of patients with CLL/SLL. In these cases, lymphoma cells appear to interact with microenvironmental Notch ligands in secondary lymphoid organs through unmutated Notch receptors, borrowing from the playbook of normal lymphocytes. Furthermore, the expression of Notch ligands by defined subsets of fibroblastic stromal cells illustrates a new paradigm through which microenvironmental signals can profoundly influence the differentiation and function of adjacent lymphoid cells. We speculate that better understanding the regulation of Notch signaling and fibroblastic stromal cells in secondary lymphoid organs will provide valuable new information with translational potential both in immunobiology and in malignant hematology. Disclosures Maillard: Genentech: Consultancy; Regeneron: Consultancy.

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Safonova, T. N., et G. V. Zaitseva. « Anti-inflammatory treatment of conjunctivitis against the background of shigellosis and chlamydia : clinical observations ». Meditsinskiy sovet = Medical Council, n^o 13 (3 septembre 2024) : 191–96. http://dx.doi.org/10.21518/ms2024-342.

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Conjunctivitis accounts for about a third of all ocular pathology in clinical ophthalmology and is the most common inflammatory lesion of the eyes. This nosology can be both infectious and non-infectious in nature. The protection of the visual organ from exogenous and endogenous antigens is carried out with the help of highly specialized lymphoid tissue associated with the eye, which belongs to the peripheral organs of the immune system. The main task of the lymphoid tissue of the eye surface, which includes the conjunctiva, is to maintain a balance between the inflammatory immune response and tolerance to non-pathogenic factors, preventing the development of a permanent inflammatory reaction. Chronic conjunctivitis develops in patients with increased sensitization to a particular antigen. The article presents various aspects of pathogenesis, clinical picture, modern diagnostic methods, as well as management tactics for patients with chronic conjunctivitis of endogenous etiology, which developed against the background of systemic infectious diseases: shigellosis and chlamydia. The clinical efficacy of a combination of antibacterial drugs using the nonsteroidal anti-inflammatory drug bromfenac has been demonstrated. With a prolonged course of chronic conjunctivitis and the absence of a positive response to local therapy, additional examination is necessary to identify possible endogenous etiological factors.

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Ocklind, G., J. Talts, R. Fässler, A. Mattsson et P. Ekblom. « Expression of tenascin in developing and adult mouse lymphoid organs. » Journal of Histochemistry & ; Cytochemistry 41, n^o 8 (août 1993) : 1163–69. http://dx.doi.org/10.1177/41.8.7687262.

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The extracellular matrix (ECM) is essential in regulating many cell functions in non-lymphoid cells, and the ECM may also play a role in the function of the immune system. Tenascin is a hexameric glycoprotein of the ECM. In mouse, two major polypeptides of MW 210 KD and 260 KD are formed by differential splicing. Northern blot screening of various mouse tissues showed that the short 6 KB tenascin message was strongly expressed in the adult thymus, whereas very little or no tenascin mRNA could be detected in spleen. In addition, immunoblotting and histological analysis with monoclonal anti-tenascin antibodies revealed the presence of tenascin in lymph nodes and spleen. In thymus, only a short-splice variant of tenascin was detected by immunoblotting, which supported the Northern blot results. Immunohistology showed that the epithelial reticular stroma in both embryonic and adult mouse thymus expressed tenascin, as did the postnatal mesenchymal reticular stroma in lymph nodes and spleen. The distribution of tenascin in the thymus was more restricted than that of fibronectin and laminin.

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Wijeyesinghe, Sathi, Lalit K. Beura, Mark J. Pierson, J. Michael Stolley, Pamela C. Rosato et David Masopust. « Quantifying the durability, expansibility, and tissue-autonomous nature of the immune system uncovers a resident reservoir for circulating immunity ». Journal of Immunology 204, n^o 1_Supplement (1 mai 2020) : 235.5. http://dx.doi.org/10.4049/jimmunol.204.supp.235.5.

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Abstract Immune cells develop in specialized lymphoid organs, but the mature immune system is integrated throughout the body and regulates tissue homeostasis and defense. This study examines how immunity persists within adult murine tissues while addressing issues of tissue autonomy, resistance to perturbations, and numerical contribution to the cellularity of visceral organs. Using quantitative immunofluorescent microscopy, we report that the immune system is expansible in nonlymphoid tissues following microbial experience, and hematopoietic cells comprise up to 30% of cells in visceral organs of laboratory mice housed in non-SPF conditions. Most hematopoietic cells in nonlymphoid tissues were autonomously maintained for >30 days, without contribution from circulation or primary lymphoid organs. Focusing on antiviral T cell immunity, we demonstrate tissue-autonomous maintenance of resident memory T cells for >200 days. Resident T cell memory was largely durable following significant environmental perturbations and de novo immune responses. Once established, resident T cells did not require the T cell receptor for survival, longevity, or retention of a poised effector-like phenotype. Ultimately, T cell memory did decay in some organs, not others, and gradually increased in circulation. Surgical separation of parabiotic mice unexpectedly revealed a tissue-resident provenance for memory T cells in peripheral blood. We propose a model whereby circulating memory T cells do not replenish resident populations, but instead a tissue-resident reservoir supports long-term maintenance of the bloodborne pool. Collectively, these data demonstrate the durability and autonomous nature of the tissue-integrated immune system.

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Articles de revues sur le sujet « Non-lymphoid organs »

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