In vivo expansion coincident with excessive in vitro cell death within the memory subset of CD8+ T cells in HIV type 1 infection

In HIV-1-infected individuals the CD8+ T cell subset is considerably expanded. This has been shown to be caused predominantly by an increase in the number of CD8+CD28- T cells. To characterize further the subsets of CD8+ T cells, we have performed analyses of cell surface phenotype, T cell receptor Vbeta usage, and ability to survive in unstimulated cultures. CD8+CD28- T cells frequently expressed CD45RA. Nonetheless, coincident expression of CD95 (Fas) and high levels of integrins suggested that these cells were immunologically experienced. Contrary to what has been observed in CD8+CD28- T cells from uninfected individuals, a common hierarchy of Vbeta usage was found in CD8+CD28- T cells from HIV-1-infected individuals, which was adhered to by all the study participants, and which was shown to be similar to that observed within CD8+CD28+ T cells. Cells from the memory subsets of CD8+ T cells showed a high incidence of spontaneous death in unstimulated cultures, indicating that these cells have received signals for death by apoptosis in vivo. In contrast, most naive CD8+CD28+CD45RA+ cells survived. The CD8+CD28- memory subset is expanded in vivo despite evidence for coincident excessive cell death in vitro. Our results are consistent with the notion that frequent transitions occur from the memory CD8+CD28+CD45RA- T cell subset to the end-stage CD8+CD28- subset during HIV-1 infection.