IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES

确定T细胞周转率具有重要意义 对我们理解T淋巴细胞动态平衡和 艾滋病的发病机制，但关于T细胞周转的信息很少 我们使用了核苷类似物溴脱氧尿苷(BrdU) 五色流式细胞术联合检测T细胞 正常和猿猴免疫缺陷病毒的淋巴细胞转化率 (SIV)感染正常动物的恒河猴T细胞 以相对较快的速度，随着记忆细胞更快地翻转 SIV感染动物体内幼稚细胞的标记与消除 CD4+和CD8+BrdU标记细胞的比率均提高了2%至 正常人群和SIV感染人群的3倍于正常对照 动物外周血中CD4+T细胞BrdU标记率与衰退率密切相关 与CD8+T细胞的清除率相关 BrdU标记细胞在幼稚和记忆T细胞中均被加速 我们的结果为SIV感染患者的淋巴细胞提供了直接的 CD_4~+和CD_8~+T细胞周转率增加的证据 艾滋病病毒感染和对我们的重要影响 T细胞动态平衡及其调控机制的研究进展 最近用BrdU标记的研究表明，艾滋病患者的CD4+T细胞耗竭 在切除胸腺的猴子身上进行了研究，并显示出类似的总体比率 BrdU的摄取和衰变，但标记率的差异 某些CD4+T细胞亚群指的是Rosenzweig M， 德玛利亚·M，哈珀·DM，弗里德里希·S，贾恩·RK，约翰逊RP提速 猴免疫缺陷时CD_4~+、CD_8~+T淋巴细胞转化率的变化 病毒感染猕猴Proc Natl Acad Science USA 1998；95：6388-6393

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