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Lymphocyte Immunophenotyping in SIV Infection
Monday, 1:30 - 3:30 pm
Background: 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.
Methods and Results: We identified 2 distinct populations of CD4+CD8+ T cells in rhesus macaques: the dominant one was CD4hiCD8low and expressed the CD8aa homodimer, while the minor population was CD4lowCD8hi and expressed the CD8ab heterodimer. Phenotypic analysis using different combinations of naïve/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 (based on Ki67 expression) 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 naïve CD4+ T cells. Intracellular cytokine staining indicated that CD4hiCD8low cells produced TNF-a and IFN-g in response to stimulation with CMV and that the frequency of CMV-specific cells was enriched in CD4hiCD8low cells compared with CD4hiCD8– 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.
Conclusions: 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.
Keywords: CD4+CD8+ Double positive T cells; SIV