Cell cycling in HIV infection: analysis of in vivo activated lymphocytes.
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 (P < 0.001 for both). The percentage levels of proliferative CD4+ CD25+, CD8+ CD25+ and CD8+ CD38+ lymphocytes were, however, similar in HIV+ patients and controls, indicating that the proliferative fraction of cells in vivo was confined to the HLA-DR+ subset and absent from the CD25+ and CD38+ populations. Four HIV+ patients had grossly elevated levels of CD8+ lymphocytes which were CD38+ (> 95%) 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.
Department of Immunology, King's College School of Medicine and Dentistry, London, UK.
M
M
Mahalingam
A
A
Pozniak
T J
TJ
McManus
D
D
Vergani
M
M
Peakman
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002453:Cell Cycle; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1