The Fas/FasL system and T cell apoptosis in HIV-1-infected lymphoid tissue during highly active antiretroviral therapy

Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. In the present study we have phenotyped apoptotic T cells in tonsillar lymphoid tissue from 11 HIV-1-infected patients by flow cytometry light-scatter characteristics during 48 weeks of highly active antiretroviral therapy (HAART). We found that the decline in tonsillar viral load was associated with a decrease in the proportion of apoptotic CD4(+) and CD8(+) T cells. CD4 cell apoptosis was predominantly seen within the memory CD28(+)Fas(+)FasL(+) population. The increased level of apoptotic CDS' T cells was found among activated Fas' memory cells irrespective of CD28 and FasL expression. These T cell subsets were expanded in untreated infection, but normalized With therapy. We conclude that HIV-1 triggers FasL-mediated apoptosis of uninfected CD4(+) T cells, whereas CD8(+) T cell apoptosis is driven by chronic immune activation. Virus suppression reverses both of these mechanisms, contributing to immune reconstitution during HAART. (C) 2001 Academic Press.