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      Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4 + T Lymphocytes from Effector Sites in the Gastrointestinal Tract

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          Abstract

          Given its population of CCR5-expressing, immunologically activated CD4 + T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4 + T cells would be observed in HIV-1–infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4 + T cells compared with peripheral blood CD4 + T cells is seen during primary HIV-1 infection. CD4 + T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4 + T cell population, a significantly greater CD4 + T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical.

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          Most cited references 38

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          Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells.

          Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.
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            An inducible transcription factor activates expression of human immunodeficiency virus in T cells.

             G Nabel,  D Baltimore (2015)
            Human immunodeficiency virus (HIV) production from latently infected T lymphocytes can be induced with compounds that activate the cells to secrete lymphokines. The elements in the HIV genome which control activation are not known but expression might be regulated through a variety of DNA elements. The cis-acting control elements of the viral genome are enhancer and promoter regions. The virus also encodes trans-acting factors specified by the tat-III and art genes. We have examined whether products specific to activated T cells might stimulate viral transcription by binding to regions on viral DNA. Activation of T cells, which increases HIV expression up to 50-fold, correlated with induction of a DNA binding protein indistinguishable from a recognized transcription factor, called NF-kappa B, with binding sites in the viral enhancer. Mutation of these binding sites abolished inducibility. That NF-kappa B acts in synergy with the viral tat-III gene product to enhance HIV expression in T cells may have implications for the pathogenesis of AIDS (acquired immune deficiency syndrome).
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              CD95's deadly mission in the immune system.

              Apoptosis in the immune system is a fundamental process regulating lymphocyte maturation, receptor repertoire selection and homeostasis. Thus, death by apoptosis is as essential for the function of lymphocytes as growth and differentiation. This article focuses on death receptor-associated apoptosis and the role of CD95 (Apo-1/Fas)-mediated signalling in T-cell and B-cell development and during the course of an immune response. Gaining an insight into these processes improves our understanding of the pathogenesis of diseases such as cancer, autoimmunity and AIDS, and opens new approaches to rational treatment strategies.
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                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                20 September 2004
                : 200
                : 6
                : 761-770
                Affiliations
                [1 ]Aaron Diamond AIDS Research Center and The Rockefeller University, New York, NY 10016
                [2 ]New York University School of Medicine, New York, NY 10016
                [3 ]Bernhard-Nocht Institut Fur Tropenmedizin, 20359 Hamburg, Germany
                Author notes

                Address correspondence to Martin Markowitz, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., 7th Fl., New York, NY 10016. Phone: (212) 448-5020; Fax: (212) 725-1126; email: mmarkowitz@ 123456adarc.org

                Article
                20041196
                10.1084/jem.20041196
                2211967
                15365095
                Copyright © 2004, The Rockefeller University Press
                Categories
                Article

                Medicine

                primary hiv-1, cd4+ t cells, galt

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