Altered ex vivo balance between CD28(+) and CB28(-) cells within HIV-specific CD8(+) T cells of HIV-seropositive patients

The CD8(+)CD28(-) cell population in the blood of HIV-infected individuals is considerably expanded. Yet the cause of this expansion is not clear. The recent demonstration of identical TCR-rearranged genes in CD8(+)CD28(+) an d CD8(+)CD28(-) expanded T cells of HIV-seropositive patients supports the hypothesis that these two subpopulations are phenotypic variants of the sam e lineage. To further elucidate the precise relationship between them, we m easured the fraction of CD28(+) and CD28(-) T cell subsets in IFN-gamma-pro ducing CD8(+) T cells by intracellular staining and cytofluorometry as a fu nctional test for ex vivo recognition of epitopes derived from HIV-1, Epste in-Barr virus (EBV) and influenza virus. HIV-specific CD8(+) T cells were p redominantly CD28- in all the eight HIV-seropositive subjects tested. In co ntrast, the anti-EBV and anti-influenza CD8(+) T cells were mainly CD28(+) in these patients as well as in HIV-seronegative individuals. This supports the notion that the CD8(+) CD28(-) hyperlymphocytosis observed in HIV infe ction is due mainly to chronic activation and differentiation of HIV-specif ic memory CD8(+)CD28(+) T cells into terminally differentiated CD8(+)CD28(- ) lymphocytes, because of intense HIV-1 replication and without any importa nt bystander activation. This clarification of the mechanisms underlying th e CD8(+) CD28(-) expansion in HIV-induced pathogenesis may have important t herapeutic implications.