Open AccessType 1/type 2 cytokine modulation of T-cell programmed cell death as a model for human immunodeficiency virus pathogenesis.
Author(s) -
Mario Clerici,
Apurva Sarin,
Robert L. Coffman,
Thomas A. Wynn,
Stephen P. Blatt,
Craig W. Hendrix,
Stanley F. Wolf,
Gene M. Shearer,
Pierre A. Henkart
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.25.11811
Subject(s) - lymphokine , programmed cell death , cytokine , biology , t cell , immunology , interleukin 2 , t lymphocyte , immune system , apoptosis , biochemistry
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.