IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES

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Defining the rate at which T cells turn over has important implications for our understanding of T lymphocyte homeostasis and AIDS pathogenesis, yet little information on T cell turnover is available We employed the nucleoside analogue bromodeoxyuridine (BrdU) in combination with five color flow cytometric analysis to evaluate T lymphocyte turnover rates in normal and simian immunodeficiency virus (SIV)-infected rhesus macaques T cells in normal animals turned over at relatively rapid rates, with memory cells turning over more quickly than naive cells In SIV-infected animals, the labeling and elimination rates of both CD4+ and CD8+ BrdU-labeled cells were increased by 2 to 3-fold as compared with normal controls In normal and SIV-infected animals, the rates of CD4+ T cell BrdU-labeling and decay were closely correlated with those of CD8+ T cells The elimination rate of BrdU-labeled cells was accelerated in both naive and memory T lymphocytes in SIV-infecte d an imals Our results provide direct evidence for increased rates of both CD4+ and CD8+ T cell turnover in AIDS virus infection and have important implications for our understanding of T cell homeostasis and the mechanisms responsible for CD4+ T cell depletion in AIDS Recent studies with BrdU labeling have been conducted in thymectomized monkeys and show similar overall rates of BrdU uptake and decay but differences in the labeling rate of certain subpopulations of CD4+ T cells REFERENCES Rosenzweig M, DeMaria M, Harper DM, Friedrich S, Jain RK, Johnson RP Increased rates of CD4+ and CD8+ T lymphocyte turnover in simian immunodeficiency virus-infected macaques Proc Natl Acad Science USA 1998; 95:6388-6393