S‐phase entry leads to cell death in circulating T cells from HIV‐infected persons

Central memory T cells are thought to play a critical role in memory T cell homoestasis by undergoing self‐renewal and by maturating into effector T cells that mediate immunity at tissue sites. Circulating T cells in S phase of the cell cycle are found at increased frequencies during HIV infection and are predominantly composed of cells with a central memory phenotype. Here, we tested the hypothesis that CD4 and CD8 S‐phase T cells have different capacities to complete cell cycle and survive. S‐phase T cells in peripheral blood from HIV‐infected donors were identified by incubating whole blood with BrdU ex vivo. Upon in vitro cultivation, S‐phase T cells were more likely to die than to complete mitotic division. Intrinsic differences were observed between CD4 and CD8 S‐phase T cells during incubation. Higher frequencies of CD4+ S‐phase T cell underwent apoptosis after incubation in medium alone or after TCR stimulation, and CD4+ S‐phase T cells were less readily induced to proliferate after incubation with IL‐2 than were CD8+ S‐phase T cells. CD4+ and CD8+ S‐phase T cells expressed low levels of Bcl‐2, which could contribute to their heightened susceptibility to cell death. Intrinsic differences in the proliferation and survival of CD4+ and CD8+ S‐phase T cells could influence the homeostatic maintenance of these T cell subsets in HIV disease.