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Title: Skin and heart allograft rejection solely by long-lived alloreactive TRM cells in skin of severe combined immunodeficient mice
Author: Tian, Qianchuan; Zhang, Zhaoqi; Tan, Liang; Yang, Fan; Xu, Yanan; Guo, Yinan; Wei, Dong; Wu, Changhong; Cao, Peng; Ji, Jiawei; Wang, Wei; Xie, Xubiao; Zhao, Yong
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 ROR gamma t 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.
Corresponding author: Zhao, Yong
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PubYear: 2022
Volume: 8
Issue: 4
Journal: Science Advances
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URL: https://www.science.org/doi/10.1126/sciadv.abk0270