In this study, we mainly investigated the expression of IFN-gamma and IL-22-producing CD4(+)T cells, the relationship between the two cytokines in human tuberculosis. We showed that IFN-gamma and IL-22 were induced by human mycobacterial infection. Besides, CD4(+)T cells expressing IFN-gamma and IL-22 were significantly elevated following PPD stimulation. In addition, IFN-gamma and IL-22 -expressing CD4(+)T cells were distinct from each other. We also found that there was a reciprocal relationship between IFN-gamma and IL-22 production. The production of IL-22 was markedly enhanced in the absence of IFN-gamma, also, the expression of IFN-gamma was increased when the IL-22 signaling was inhibited by monoclonal anti-IL-22 mAb. Furthermore, data revealed that the detectable IL-22 affected the phynotype of IFN-gamma(+)CD4(+)T cells. IL-22 induced upregulation of CD27 expression in IFN-gamma(+)CD4(+)T cells, which might further confirm that IL-22 had an effect on the response of IFN-gamma. Thus, this work provides a previous unknown relationship between IFN-gamma and IL-22 in human TB disease. (c) 2012 Elsevier B.V. All rights reserved.