M. Clerici et al., TYPE-1 TYPE-2 CYTOKINE MODULATION OF T-CELL PROGRAMMED CELL-DEATH AS A MODEL FOR HUMAN-IMMUNODEFICIENCY-VIRUS PATHOGENESIS, Proceedings of the National Academy of Sciences of the United Statesof America, 91(25), 1994, pp. 11811-11815
In vitro T-cell receptor-induced programed cell death in both activate
d 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 in
terferon gamma and interleukin 2 (IL-2), as well as the macrophage-pro
duced IL-12, which favor cell-mediated T-cell responses, blocks both s
ystems 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 c
ell death. A role for endogenously produced cytokines was suggested by
the inhibition of T-cell receptor-mediated death by antibodies agains
t IL-4 and IL-10 and its enhancement by anti-IL-12 in cultures contain
ing monocytes. These results demonstrate that the functional propertie
s of type 1 and type 2 cytokine classes may be further extended to inc
lude their effects on T-cell programed cell death and their possible r
ole in the pathogenesis of HIV infection.