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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在人和几种动物的外周血中已经描述了共表达CD 4+和CD 8+的循环T淋巴细胞。然而，CD 4 + CD 8 + T细胞的起源和功能特性仍然知之甚少。我们在恒河猴中鉴定了2个不同的CD 4 + CD 8 + T细胞群体：占主导地位的是CD 4 hiCD 8low，表达CD 8 α α同源二聚体，而次要群体是CD 4lowCD 8hi，表达CD 8 α β异源二聚体。使用幼稚/记忆和活化标记物的不同组合进行的表型分析表明，CD 4 hiCD 8low T细胞表现出效应记忆表型（CD 28 <$CD62 L <$Fas+），被活化（HLA-DR+），并且以比单一阳性CD 4 + T细胞更高的速率增殖。此外，它们表达相对低水平的CD 7和相对高水平的颗粒酶B。实时PCR分析显示，CD 4 hiCD 8low细胞中TCR重排切除DNA环的水平低于幼稚CD 4 + 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CD 4 hiCD 8low T细胞水平较低，这一观察结果得到了SIV感染动物前瞻性研究的证实。总之，这些数据表明，CD 4 hiCD 8low T细胞代表效应记忆CD 4 + T细胞的独特群体，并且该细胞群体在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.