Cell cycling in HIV infection: analysis ofin vivoactivated lymphocytes

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Abstract
SUMMARY: Infection with HIV results in increased circulating levels of T lymphocytes expressing phenotypic markers of immune activation. In the present study, using three-colour immunofluorescence, we examined the cell cycle status of these activated cells. Activated (HLA-DR+ CD25+ and CD38+) CD4+ and CD8+ T lymphocytes in peripheral blood were analysed for DNA content in 15 HIV + patients and 10 healthy age- and sex-matched control subjects. As expected, all HIV+ patients had elevated percentage levels of activated CD4+ HLA-DR+, CD4+ CD25+ CD8+ HLA-DR+ CD8+ CD25+ and CD8+ CD38+ T lymphocytes compared with control subjects (P<0.001 for all). Percentage levels of CD4+ HLA-DR+ and CD8+ HLA-DR+ T lymphocytes in the ‘proliferative’(S-G2M) phase of the cell cycle were also higher in the HIV+” patients compared with controls (P95%) and confined to the pre-G0-G1 phase of the cell cycle, suggesting these may be cells committed to apoptosis. These observations indicate an increase in the proliferative capacity of HLA-DR+ T lymphocytes in HIV infection in vivo. The reduced DNA content in other populations (e.g. CD38+ CD8+ lymphocytes) of some patients with advanced HIV disease suggests that these cells are apoptotic. Thus our results define both proliferative and apoptotic processes as a spectrum of activation-related events in HIV infection.

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