Increased CD95/Fas-induced apoptosis of HIV-specific CD8+ T cells

Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8+ T cells express the CD45RA(-)CD62L(-) but lack the CD45RA(+)CD62L- T cell effector memory (T-EM) phenotype. This skewing is not found in CMV- and EBV-specific CD8(+) T cells in HIV-infected individuals. CD95/Fas-induced apoptosis is much higher in the CD45RA-CD62L- T-EM cells. However, cytotoxicity and IFN gamma production by HIV-specific CD8(+) T cells is not impaired. Our data suggest that the survival and differentiation of HIV-specific CDW T cells may be compromised by CD95/Fas apoptosis induced by FasL-expressing HIV-infected cells.