IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES

恒河猴 T 细胞更新的体内分析

• 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
• 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

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细胞翻转的速率很重要 对我们理解T淋巴细胞稳态的影响， 艾滋病发病机制，但很少有关于T细胞周转的信息， 我们使用核苷类似物溴脱氧尿苷（BrdU） 结合五色流式细胞术分析评价T 正常和猴免疫缺陷病毒的淋巴细胞更新率 （SIV）感染恒河猴T细胞在正常动物中翻转 以相对较快的速率，其中存储器单元更快地翻转 在SIV感染的动物中， CD 4+和CD 8 + BrdU标记细胞的比率增加2， 3-在正常和SIV感染者中， 动物，CD 4 + T细胞BrdU标记率和衰变率密切相关 与CD 8 + T细胞的清除率相关。 BrdU标记的细胞在初始和记忆T细胞中均被加速， SIV感染动物的淋巴细胞我们的结果提供了直接的 有证据表明，CD 4+和CD 8 + T细胞更新率增加， 艾滋病病毒的感染，并有重要的影响， 了解T细胞稳态和负责的机制 艾滋病中的CD 4 + T细胞耗竭 在切除胸腺的猴子中进行， 的BrdU吸收和衰变，但在标记率的差异， CD 4 + T细胞的某些亚群 DeMaria M，哈珀DM，Friedrich S，Jain RK，约翰逊RP 猴免疫缺陷病中CD 4+和CD 8 + T淋巴细胞转换的研究 病毒感染的猕猴美国国家科学院学报1998; 95：6388-6393