PHENOTYPIC & FUNCTIONAL CHARACTERIZATION CD4+/CD8+ DP T LYMPHOCYTES IN MONKEYS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。循环T淋巴细胞共表达CD4+和CD8+已在人类和几种动物的外周血中被描述。然而，CD4+CD8+ T细胞的起源和功能特性仍然知之甚少。我们在恒河猴体内发现了两种不同的CD4+CD8+ T细胞群体：显性群体为CD4hiCD8low，表达CD8 α - α二聚体；次要群体为CD4lowCD8hi，表达CD8 α - β异源二聚体。使用na - ve/memory和激活标记物的不同组合进行表型分析表明，CD4hiCD8low T细胞表现出效应记忆表型（CD28¿CD62L¿Fas+），被激活（HLA-DR+），并且比单一阳性CD4+ T细胞增殖率更高。此外，它们表达相对低水平的CD7和相对高水平的颗粒酶b。实时PCR分析显示，CD4hiCD8low细胞中tcr重排切除DNA环的水平低于正常CD4+ T细胞。横断面研究显示，与未感染的对照组相比，siv感染动物的CD4hiCD8low T细胞水平较低，这一观察结果得到了siv感染动物的前瞻性研究的证实。综上所述，这些数据表明CD4hiCD8low T细胞代表了一种不同的效应记忆CD4+ T细胞群，并且这种细胞群在SIV感染过程中被耗尽。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Circulating T lymphocytes co-expressing CD4+ and CD8+ have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of CD4+CD8+ T cells remain poorly understood. We identified 2 distinct populations of CD4+CD8+ T cells in rhesus macaques: the dominant one was CD4hiCD8low and expressed the CD8 alpha alpha homodimer, while the minor population was CD4lowCD8hi and expressed the CD8 alpha beta heterodimer. Phenotypic analysis using different combinations of na¿ve/memory and activation markers indicated that CD4hiCD8low T cells exhibited an effector memory phenotype (CD28¿CD62L¿Fas+), were activated (HLA-DR+), and proliferated at a higher rate than single positive CD4+ T cells. Furthermore, they expressed relatively low levels of CD7 and relatively high levels of granzyme B. Real-time PCR analysis revealed lower levels of TCR-rearrangement excisional DNA circles in CD4hiCD8low cells than in na¿ve CD4+ T cells. Cross-sectional studies revealed lower levels of CD4hiCD8low T cells in SIV-infected animals compared to uninfected controls, an observation borne out by prospective studies of SIV-infected animals. Taken together, these data suggest that CD4hiCD8low T cells represent a distinct population of effector memory CD4+ T cells and that this cell population is depleted during the course of SIV infection.