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

In HIV-1-infected individuals the CD8(+) T cell subset is considerably expa nded. 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 r eceptor VP usage, and ability to survive in unstimulated cultures. CD8(+)CD 28(-) T cells frequently expressed CD45RA, Nonetheless, coincident expressi on of CD95 (Fas) and high levels of integrins suggested that these cells we re immunologically experienced. Contrary to what has been observed in CD8()CD28(-) T cells from uninfected individuals, a common hierarchy of VP usag e 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 si milar 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 u nstimulated 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 despit e evidence for coincident excessive cell death ill vitro. Our results are c onsistent with the notion that frequent transitions occur from the memory C D8(+)CD28(+)CD45RA(-) T cell subset to the end-stage CD8(+)CD28(-) subset d uring HIV-1 infection.