IL-12 INDUCES HUMAN T-CELLS SECRETING IL-10 WITH IFN-GAMMA

A clear differentiation of Th1 and Th2 cytokine-secreting subsets in h umans has not yet been defined, To further examine cytokine-directed d ifferentiation of human T cell responses to both exogenous and autoant igens, we generated 346 short term T cell lines at limiting dilutions from six normal individuals to tetanus toroid and myelin basic protein in the presence of IL-2 with or without the addition of IL-12 and ant i-IL-4 mAb. T cell lines were examined for [H-3]thymidine incorporatio n and cytokine secretion of IFN-gamma, IL-4, and IL-10. After culture in the presence of IL-12 and anti-IL-4 mAb, the predominant T cell res ponse to Ag stimulation was simultaneous secretion of IL-10 and IFN-ga mma. The concomitant secretion of IL-10 and IFN-gamma by T cells was c onfirmed by stimulating lines in the absence of APCs with plate-bound anti-CD3 mAb after two rounds of Ag-specific stimulation. Moreover, IL -12 enhanced IL-10 and IFN-gamma production in a myelin basic protein- reactive T cell clone, demonstrating that a differentiated T cell clon e could be induced to secrete both cytokines, The addition of a neutra lizing anti-IFN-gamma Ab to cultures with IL-12 and anti-IL-4 mAb duri ng the generation of tetanus toxoid-reactive lines had no effect on th e induction of IL-10 and IFN-gamma secretion, indicating that IL-12 an d not IFN-gamma was responsible for the induction of this subset of T cells, Thus, in human T cells, IL-12 induces concomitant secretion of IL-10 and IFN-gamma.