IL-10 efficiently blocks the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway [24], as well as indirectly by downregulating the function of antigen-presenting cells. To elucidate the resistance of CD4+ T cells to this direct inhibition in RA, we investigated the production of IFN-γ after CD3 and CD28 costimulation in the presence of IL-10, the induction of STAT1 and STAT3 phosphorylation by IL-10, and the expression of SOCS1 and SOCS3 mRNA in peripheral blood (PB) CD4+ T cells from RA patients.