IL-2 INDUCES FAS LIGAND FAS (CD95L CD95) CYTOTOXICITY IN CD8(+) AND CD4(+) T-LYMPHOCYTE CLONES/

IL-2 is a T cell growth factor that has pleiotropic functions in T cel l differentiation, induction of lymphokine-activated killer cells, and regulation of immune responses, In studying TCR triggering of perfori n or Fas ligand (FasL)/Fas (CD95 ligand/CD95) cyto toxicity in our inf luenza-specific T cell clones, we found that IL-2 can also induce FasL /Fas cytoxicity, IL-2 induces FasL/Fas cytotoxicity in our CD8(+) and CD4(+) Th1 clones, but not in our CD4(+) Th2 clones, IL-2 induction of cytolytic activity occurs when the CD8(+) T cells are refractory to I L-2-induced proliferation, This killing is Ag independent, MHC unrestr icted, and blocked by Fas.Fc fusion protein, IL-2 induces FasL/Fas cyt otoxicity in a dose-dependent manner, but does not induce high levels of FasL expression as detected by flow cytometry. TCR triggered FasL/F as cytotoxicity is detectable in CD8(+) and Th1 clones by 3 h and peak s at 6 h; high levels of killing are maintained for at least 24 h, Sim ilarly, IL-2 induces FasL/Fas killing in CD8(+) and Th1 clones within 3 h of stimulation and maintains high levels for at least 24 h, TCR-tr iggered FasL/Fas killing is inhibited by emetine and cyclosporin A, wh ereas IL-2-induced FasL/Fas killing is inhibited by emetine, but not b y cyclosporin A, These results demonstrate a second mechanism to induc e FasL/Fas cytotoxicity in CD8(+) and Th1 clones and may explain IL-2 induction of Ag-independent MHC-unrestricted lymphokine-activated kill er cell activity.