This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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 (CD28CD62LFas+), 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.
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