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

Abstract

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+ and CD8+ CD28− expanded T cells of HIV-seropositive patients supports the hypothesis that these two subpopulations are phenotypic variants of the same lineage. To further elucidate the precise relationship between them, we measured the fraction of CD28+ and CD28− T cell subsets in IFN-γ-producing CD8+ T cells by intracellular staining and cytofluorometry as a functional test for ex vivo recognition of epitopes derived from HIV-1, Epstein-Barr virus (EBV) and influenza virus. HIV-specific CD8+ T cells were predominantly CD28− in all the eight HIV-seropositive subjects tested. In contrast, 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 infection is due mainly to chronic activation and differentiation of HIV-specific memory CD8+ CD28+ T cells into terminally differentiated CD8+ CD28− lymphocytes, because of intense HIV-1 replication and without any important bystander activation. This clarification of the mechanisms underlying the CD8+ CD28− expansion in HIV-induced pathogenesis may have important therapeutic implications.