Differentiation,distribution and γδ T cell-driven regulation of IL-22-producing T cells in tuberculosis

Differentiation,distribution and immune regulation of human il-22-producing t cells in infections remain unknown. here,we demonstrated in a nonhuman primate model that m. tuberculosis infection resulted in apparent increases in numbers of t cells capable of producing il-22 de novo without in vitro ag stimulation,and drove distribution of these cells more dramatically in lungs than in blood and lymphoid tissues. consistently,il-22-producing t cells were visualized in situ in lung tuberculosis (tb) granulomas by confocal microscopy and immunohistochemistry,indicating that mature il-22-producing t cells were present in tb granuloma. surprisingly,phosphoantigen hmbpp activation of vγ2vδ2 t cells down-regulated the capability of t cells to produce il-22 de novo in lymphocytes from blood,lung/bal fluid,spleen and lymph node. up-regulation of ifnγ-producing vγ2vδ2 t effector cells after hmbpp stimulation coincided with the down-regulated capacity of these t cells to produce il-22 de novo. importantly,anti-ifnγ neutralizing ab treatment reversed the hmbpp-mediated down-regulation effect on il-22-producing t cells,suggesting that vγ2vδ2 t-cell-driven ifnγ-networking function was the mechanism underlying the hmbpp-mediated down-regulation of the capability of t cells to produce il-22. these novel findings raise the possibility to ultimately investigate the function of il-22 producing t cells and to target vγ2vδ2 t cells for balancing potentially hyper-activating il-22-producing t cells in severe tb. © 2010 yao et al.