Type 1/type 2 cytokine modulation of T-cell programmed cell death as a model for human immunodeficiency virus pathogenesis.
In vitro T-cell receptor-induced programmed cell death in both activated T cells from human immunodeficiency virus-seronegative (HIV-) donors and resting T cells from HIV+ donors was substantially influenced by cytokines. Addition of exogenous recombinant "type 1" lymphokines interferon gamma and interleukin 2 (IL-2), as well as the macrophage-produced IL-12, which favor cell-mediated T-cell responses, blocks both systems of T-lymphocyte programmed cell death. In contrast, the "type 2" lymphokines IL-4 and IL-10, which favor antibody responses, either had no effect or enhanced these systems of in vitro T-cell programmed cell death. A role for endogenously produced cytokines was suggested by the inhibition of T-cell receptor-mediated death by antibodies against IL-4 and IL-10 and its enhancement by anti-IL-12 in cultures containing monocytes. These results demonstrate that the functional properties of type 1 and type 2 cytokine classes may be further extended to include their effects on T-cell programmed cell death and their possible role in the pathogenesis of HIV infection.
Clerici
M
M
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Sarin
A
A
Coffman
R L
RL
Wynn
T A
TA
Blatt
S P
SP
Hendrix
C W
CW
Wolf
S F
SF
Shearer
G M
GM
Henkart
P A
PA
D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology* / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D006678:HIV / Q000472:pathogenicity*; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008954:Models, Biological; D011994:Recombinant Proteins / Q000494:pharmacology
D016207:Cytokines; D007378:Interleukins; D011994:Recombinant Proteins; D007371:Interferon-gamma