EARLY EFFECTS OF SIV INFECTION ON GUT ASSOCIATED LYMPHOID TISSUES

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The majority of the lymphocytes in the body are located in the gastrointestinal tract A large percentage of these lymphocytes are activated CD4+ T cells and are prime targets for SIV/HIV persistence and replication Intestinal lymphocytes and/or their cytokines are thought to play a major role in maintaining the structure and function of the intestinal mucosa Alterations in the composition of GALT could induce physiologic changes in intestinal function and may be responsible for the syndrome known as AIDS enteropathy To examine this hypotheses, we are examining morphologic and phenotypic changes in the intestinal tract of SIV-infected macaques Twelve rhesus monkeys were intravenously inoculated with SIVmac239 and sacrificed at 3, 7, 14, 21, and 50 days postinoculation Lymphocytes were isolated from peripheral lymph nodes, blood, spleen, and the epithelium and lamina propria of the jejunum, ileum, and colon, and analyzed by 4-color flow cytometry for CD2, 3, 4, 8 , 20, 25, 28, 34, 38, 45RA, 56, Leu-8,k TCR, and HLA-DR expression Adjacent sections were analyzed for virus-infected cells by in situ hybridization Within 14 days pi, profound drops in the proportion of CD4+ lymphocytes were observed in the intestine as compared to peripheral lymphoid tissues Increased percentages of CD8+ cells with DR+38+ and CD56+CD38+ phenotypes were observed both in intestinal and peripheral lymphoid tissue by day 7 pi In situ hybridization revealed that these changes correlated with peak viral load in the intestine This data indicates that infection of the gastrointestinal tract with SIV results in marked changes in the proportions of intestinal lymphocyte subsets Furthermore, changes in the GALT are far more pronounced than in peripheral lymphoid tissue Finally, changes in intestinal lymphocyte subsets are most likely associated with marked alterations in intestinal function which could result in malabsorption, nutritional deficiencies, and/or inc reased susceptibility of the intestine to opportunistic infection Publications Veazey RS, Lackner AA The gastrointestinal tract and the pathogenesis of AIDS AIDS 12(Suppl ) A):S35-42, 1998 Veazey RS, DeMaria MA, Chalifoux LV, Shvetz D, Pauley D, Knight HL, Rosenzweig M, Johnson RP, Desrosiers RC, Lackner AA The gastrointestinal tract as a major site of CD4+ lymphocyte depletion and viral replication in primary SIV infection Science, 180:427-431, 1998