CYTOKINE-INDUCED SURVIVAL OF ACTIVATED T-CELLS IN-VITRO AND IN-VIVO

Many antigen-specific T cells die after exposure to antigen in animals . These cells also die if they are isolated from animals shortly after activation and cultured, Various cytokines were tested for their abil ity to interfere with this in vitro death, Surprisingly, tumor necrosi s factor a and other inflammatory cytokines did not prevent the in vit ro death of activated T cells, even though these cytokines do prevent activated T cell death in animals, Therefore, the inflammatory cytokin es probably act on T cells in vivo via an intermediary factor, Four cy tokines, interleukin (IL)-2, IL-3, IL-7, and IL-15, did prevent activa ted T cell death in vitro, with IL-4 and IL-15 more effective than IL- 2 or IL-7. These cytokines share a component of their receptors, the c ommon gamma chain, gamma c. Therefore, their collective ability to pro tect activated T cells from death mag be mediated by signals involving gamma c, To assess their activity in vivo, two of the cytokines, IL-2 and IL-4, were expressed in animals at local sites of superantigen re sponses. Both cytokines increased the numbers of T cells found al the local sites 14 days later. Interleukin 4 was more effective than IL-2, even though IL-2 stimulates T cell proliferation better than IL-il. T his result suggested that IL-4 and related cytokines can promote T cel l survival in vivo as well as in vitro. The ability of these cytokines to prevent the death of activated T cells mar be important at certain stages of immune responses in animals.