INTERACTION OF IL-1-BETA, IL-6 AND TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IN HUMAN T-CELLS ACTIVATED BY MURINE ANTIGENS

We used a mixed leucocyte culture between human T cells and irradiated murine splenocytes which allowed us to distinguish between cytokine production from the responder and stimulator cells by the use of species-specific assays for mRNA up-regulation. Using this model of T cell activation by antigen, we studied the effects of human antigen-presenting cell-derived cytokines IL-1beta, IL-6 and TNF-alpha on the activation of human T cell subsets. We show in this system that exogenously added IL-1beta, IL-6 and TNF-alpha induces IL-2 receptor (R) up-regulation and IL-2 production, and proliferation by both CD4+ and CD8+ cells. The addition of IL-1beta induces IL-6 mRNA, and anti-IL-1 antibodies or an IL-IR antagonist protein completely suppresses IL-6 and TNF-alpha supported proliferation. Similarily, addition of IL-6 or TNF-alpha induces up-regulation of IL-1beta mRNA. However, anti-IL-6 and anti-IL-6R antibodies only partially block proliferation supported by IL-1beta. These findings suggest that IL-6 and TNF-alpha will induce IL-2R up-regulation/IL-2 secretion via the induction of IL-1beta production.