IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES

恒河猴 T 细胞更新的体内分析

基本信息

批准号：
6591317
负责人：
M ROSENZWEIG
金额：
$ 11.11万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2003-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6591317
关键词：
AIDS Mammalia communicable diseases hematology immunology inflammation lymphatic system technology /technique virus

项目摘要

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

定义T细胞翻转的速率具有重要对我们对T淋巴细胞稳态的理解的影响艾滋病发病机理，但关于T细胞更新的信息很少我们使用核苷类似物溴脱氧尿苷（BRDU）结合五种颜色流式细胞仪分析来评估T 淋巴细胞的转换率正常和猿猴免疫缺陷病毒（SIV）正常动物中感染的恒河猕猴T细胞转过来以相对较快的速度，记忆细胞更快地翻转比SIV感染动物中的天真细胞，标记和消除 CD4+和CD8+ BRDU标记的细胞的发生率增加了2 与正常和SIV感染的正常对照相比，3倍动物，CD4+ T细胞BRDU标记和衰减的速率紧密与CD8+ T细胞的消除率相关 Brdu标记的细胞在幼稚和记忆中都加速了 SIV感染的淋巴细胞我们的结果提供了直接的证据表明CD4+和CD8+ T细胞周转率增加的证据艾滋病病毒感染，对我们有重要影响了解T细胞稳态和负责的机制 AIDS中的CD4+ T细胞耗竭最近使用BRDU标记的研究具有是在胸腺切除猴子中进行的，显示了相似的总比率 Brdu摄取和衰减的标签率差异 CD4+ T细胞的某些亚群参考Rosenzweig M， Demaria M，Harper DM，Friedrich S，Jain RK，Johnson RP提高了费率 CD4+和CD8+ T淋巴细胞的转换率病毒感染的猕猴Proc Natl Acad Science USA 1998; 95：6388-6393