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 programed 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 programed 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 programed 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 programed cell death and their possible role in the pathogenesis of HIV infection.