Skin and heart allograft rejection solely by long-lived alloreactive T <sub>RM</sub> cells in skin of severe combined immunodeficient mice
Qianchuan Tian, Zhaoqi Zhang, Liang Tan, Fan Yang, Yanan Xu, Yinan Guo, Dong Wei, Changhong Wu, Peng Cao, Jiawei Ji, Wei Wang, Xubiao Xie, Yong Zhao
Abstract
Whether induced tissue-resident memory T (T RM ) cells in nonlymphoid organs alone can mediate allograft rejection is unknown. By grafting alloskin or heart into severe combined immunodeficient or Rag2KO mice in which a piece of induced CD4 + and/or CD8 + T RM cell–containing MHC-matched or syngeneic skin was transplanted in advance, we addressed this issue. The induced CD4 + T RM cells in the skin alone acutely rejected alloskin or heart grafts. RNA-seq analysis showed that induced CD4 + T RM cells in skin favorably differentiated into T H 17-like polarization during the secondary immune response. Inhibition of the key T H 17 signaling molecule RORγt attenuated T RM cell–mediated graft rejection. Thus, we offer a unique mouse model to specifically study T RM cell–mediated allograft rejection without the involvement of lymphocytes in lymphoid organs and tissues. Our study provides strong evidence supporting the hypothesis that long-lived alloreactive T RM cells resident in other organs/tissues substantially contribute to organ allograft rejection.