Programmed cell death induced by HIV type 1 antigen stimulation is associated with a decrease in cytotoxic T lymphocyte activity in advanced HIV type 1 infection.
The immune competence of peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus-seropositive (HIV+) patients was studied by assessing cytotoxic T lymphocyte (CTL) activity following recall HIV antigen stimulation. Target cells were HLA-A-matched EBV-transformed B cells expressing HIV-1 antigen. In the presence of recombinant IL-2 (rIL-2, 2 or 10 U/ml), about 50% of PBMCs from HIV+ asymptomatic patients responded to HIV-1 antigen stimulation in vitro with increased cytotoxic activity. In contrast, PBMCs from patients with overt AIDS, cultured in medium containing rIL-2 (2 U/ml) and HIV-1 antigen, showed no increase in cytotoxic activity; in the presence of rIL-2 (10 U/ml) and HIV-1 antigen, an inhibitory effect on CTL activity was observed. This inhibitory effect was associated with programmed cell death (apoptosis) of CD8+ lymphocytes and cells of both gamma/delta TcR-positive and -negative phenotypes. However, prior to the apoptosis, different TcR phenotypes of T lymphocyte reacted differently to HIV-1 antigen stimulation. The HIV-1 antigen initially appeared to cause gamma/delta TcR-positive T lymphocytes to proliferate and/or differentiate and later induced cell death. Whereas, prior to the apoptosis, no proliferation of gamma/delta TcR-negative T lymphocytes induced by HIV-1 antigen was observed.
Chia
W K
WK
Department of Microbiology, University of Toronto, Ontario, Canada.
Freedman
J
J
Li
X
X
Salit
I
I
Kardish
M
M
Read
S E
SE
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015488:HIV Antigens / Q000276:immunology* / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015488:HIV Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins