Skin and heart allograft rejection solely by long-lived alloreactive T<sub>RM</sub> cells in skin of severe combined immunodeficient mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35080985.
- Also identified by DOI 10.1126/sciadv.abk0270 and PMC identifier 8791614.
- Licence recorded as CC BY-NC.
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Abstract
Whether induced tissue-resident memory T (T<sub>RM</sub>) 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<sup>+</sup> and/or CD8<sup>+</sup> T<sub>RM</sub> cell-containing MHC-matched or syngeneic skin was transplanted in advance, we addressed this issue. The induced CD4<sup>+</sup> T<sub>RM</sub> cells in the skin alone acutely rejected alloskin or heart grafts. RNA-seq analysis showed that induced CD4<sup>+</sup> T<sub>RM</sub> cells in skin favorably differentiated into T<sub>H</sub>17-like polarization during the secondary immune response. Inhibition of the key T<sub>H</sub>17 signaling molecule RORγt attenuated T<sub>RM</sub> cell-mediated graft rejection. Thus, we offer a unique mouse model to specifically study T<sub>RM</sub> 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<sub>RM</sub> cells resident in other organs/tissues substantially contribute to organ allograft rejection.