FUNCTIONAL INTERACTION BETWEEN TGF-BETA AND IL-12 IN HUMAN PRIMARY ALLOGENEIC CYTOTOXICITY AND PROLIFERATIVE RESPONSE

IL-12 is an important cytokine in the control of cell-mediated immunit y, We have investigated the functional interaction of IL-12 with TGF-b eta(1), a cytokine involved in the regulation of growth and differenti ation of immunocompetent cells, during human allogeneic response devel opment, Using primary MLR, our data show that addition of exogenous TG F-beta at the sensitizing phase of the primary MLR resulted in the inh ibition of both allogeneic cytotoxic and proliferative responses, The inhibitory effect of TGF-beta on allogeneic response involves an abrog ation of IL-12/p70 production upon allostimulation, In contrast to its effect on IL-12 production, TGF-beta did not alter the expression of IL-12R beta(1)-chain (IL-12R beta) in T cells induced upon allogeneic activation, Addition of exogenous IL-12 or IFN-gamma in the MLR cultur es in the presence of TGF-beta did not result in reversal of CTL gener ation and T cell proliferation, Interestingly, TGF-beta was efficient in down-regulating IL-12 responsiveness of alloactivated T cells as we ll as TCR-alpha beta or TCR-gamma delta alloreactive T cell clones, Th ese studies suggest that the inhibitory effect of TGF-beta on the deve lopment of human allogeneic proliferation and cytotoxic responses invo lves an additional mechanism associated with an interference with IL-1 2 pathway.