Next Generation Sequencing Facilitates Quantitative Analysis of TRM Transcriptomes

Tissue-resident memory T (TRM) cells play an important role in local immunosurveillance to defense against pathogen infection and participate in many diseases. However, whether the formed TRM cells in non-lymphoid organs or tissues alone could mediate other allogeneic organ graft rejection are unknown. Here, by grafting allogeneic skin or heart to a severe combined immunodeficient (SCID) mice or Rag2 KO mice in which a piece of induced CD4 and/or CD8 TRM cells containing MHC matched or syngeneic skin was transplanted in advance, we studied the ability of these TRM cells resident in skin to reject allo-grafts in vivo. RNA seq analysis and cytology experiments showed that the induced CD4 TRM cells in skin favorably differentiated into Th17 like functional polarization during the secondary immune response. Inhibition of the key Th17 signaling molecule RORgt significantly attenuated TRM cells-mediated graft rejection and prolonged the skin allo-graft survival to a certain extent.