EVIDENCE THAT RAPAMYCIN INHIBITS INTERLEUKIN-INDUCED PROLIFERATION OFACTIVATED T-LYMPHOCYTES

Interleukin 12 is a heterodimeric cytokine involved in the regulation of natural killer cell. and T lymphocyte responses. In previous studie s, we found that IL-12 induces proliferation of T cells only after cos timulation with lectin, alloantigen, or anti-CD3 antibody. The IL-2-me diated proliferation of long-term T cell lines generated in this fashi on is typically insensitive to the immunosuppressive agent, cyclospori ne but sensitive to rapamycin. In this study, we examined the effect o f cyclosporine and rapamycin on T cells responsive to IL-12. For long- term cultured T cell lines stimulated with phytohemagglutinin, alloant igen, or solid-phase anti-CD3 antibody, rapamycin blocked IL-12-induce d proliferation to background levels. Culture in cyclosporine produced minimal inhibition of IL-12-induced T cell proliferation. Freshly iso lated CD3(+) cells did not proliferate in response to IL-12, nor did c ulture of these cells in IL-12 lead to upregulation of IL-2 receptor. These data suggest that the effect of IL-12, an important growth regul ator for activated T lymphocytes, may involve late cellular activation events.