The study was aimed to find out whether T cells with a regulatory profile could regulate the secretion of IgG4. Using tetanus Ag we found that PBMC of healthy human donors responded to exogenous IL-10 by down-regulating IgG1 and increasing IgG4 secretion. IgE was not affected. To investigate the direct effect of IL-10-producing T cells on B cells, we generated T cell clones (TCC) with two different cytokine profiles: first, IL-10 high, IL-2 low, IL-4 low TCC, and second, IL-10 low, IL-2 high, IL-4 high. The T cell-dependent Ab secretion was measured by coculturing purified CD19+ B cells and the TCC. Interestingly, we found that IgG4 production in the coculture correlated with the TCC production of IL-10 (r 2= 0.352, p= 0.0001), but not with IL-2, IL-4, nor IFN-γ. IgE showed only a trend with regard to IL-4. Further, there was decreased Ab secretion in the absence of TB cell contact. IL-10 also induced IgG4 when added to a Th1 TCC-B cell coculture system. The present study thus shows that in TB cell coculture, IL-10, if induced by the TCC or added to the system, down-regulates the immune response by inducing IgG4 secretion. This establishes a direct implication of IL-10 in humoral hyporesponsiveness, particularly in compartments where the TB cell interplay determines the subsequent immune response. The correlation between IgG4 and IL-10 (r 2= 0.352) indicates that IL-10 is an important but not the only factor for IgG4 induction.