IL-12 induces human T cells secreting IL-10 with IFN-gamma

Abstract

A clear differentiation of Th1 and Th2 cytokine-secreting subsets in humans has not yet been defined. To further examine cytokine-directed differentiation of human T cell responses to both exogenous and autoantigens, we generated 346 short term T cell lines at limiting dilutions from six normal individuals to tetanus toxoid and myelin basic protein in the presence of IL-2 with or without the addition of IL-12 and anti-IL-4 mAb. T cell lines were examined for [3H]thymidine incorporation 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 response to Ag stimulation was simultaneous secretion of IL-10 and IFN-gamma. The concomitant secretion of IL-10 and IFN-gamma by T cells was confirmed 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 clone could be induced to secrete both cytokines. The addition of a neutralizing anti-IFN-gamma Ab to cultures with IL-12 and anti-IL-4 mAb during the generation of tetanus toxoid-reactive lines had no effect on the induction of IL-10 and IFN-gamma secretion, indicating that IL-12 and 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.