论文题目：Skin and heart allograft rejection solely by long-lived alloreactive TRM cells in skin of severe combined immunodeficient mice

作者：Tian Q, Zhang Z, Tan L, Yang F, Xu Y, Guo Y, Wei D, Wu C, Cao P, Ji J, Wang W, Xie X, Zhao Y

日期：2022.1

发表期刊：Sci Advan.

doi：10.1126/sciadv.abk0270

摘要：

    Whether induced tissue-resident memory T (TRM) 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+ TRM cell-containing MHC-matched or syngeneic skin was transplanted in advance, we addressed this issue. The induced CD4+ TRM cells in the skin alone acutely rejected alloskin or heart grafts. RNA-seq analysis showed that induced CD4+ TRM cells in skin favorably differentiated into TH17-like polarization during the secondary immune response. Inhibition of the key TH17 signaling molecule RORγt attenuated TRM cell-mediated graft rejection. Thus, we offer a unique mouse model to specifically study TRM 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 TRM cells resident in other organs/tissues substantially contribute to organ allograft rejection.