ROLE OF INTERLEUKIN-6 IN THE GENERATION OF HUMAN CYTOLYTIC T-CELL CLONES

The maturation of cytolytic T lymphocytes from non-lytic precursors requires cytokines other than IL-2. Interleukin-6 is the principal cytokine that cooperates with IL-2 in the induction of CTL differentiation from murine and human thymocyte precursors. However, a cytotoxic differentiation factor role for IL-6 on mature T cells is challenged by data that indicate that IL-2 alone is sufficient for CTL generation. The aim of this study was to identify a model system in which IL-6 acted as a CDF for human peripheral T cells. Experiments that compared the cytolytic function of CTL clones cultured with and without IL-6 demonstrated that IL-6 contributes to the cytolytic activity of human CTL clones. We also demonstrate that IL-6 is endogenously produced by CTL clones in the course of their expansion with APC, lectin and IL-2. The majority of both CD4+ and CD8+ clones produced IL-6 in response to relatively high doses of IL-2. Our data suggest that IL-6 acts in an autocrine fashion to support CTL differentiation in human T-cell clones.