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    The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to Teff/TRM clusters in association with rejection. By integrating pre- and post-transplantation (Tx) mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in the human gut, providing novel insight into TRM biology. © 2023 Fu et al.


    Jianing Fu, Zicheng Wang, Mercedes Martinez, Aleksandar Obradovic, Wenyu Jiao, Kristjana Frangaj, Rebecca Jones, Xinzheng V Guo, Ya Zhang, Wan-I Kuo, Huaibin M Ko, Alina Iuga, Constanza Bay Muntnich, Adriana Prada Rey, Kortney Rogers, Julien Zuber, Wenji Ma, Michelle Miron, Donna L Farber, Joshua Weiner, Tomoaki Kato, Yufeng Shen, Megan Sykes. Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes. The Journal of experimental medicine. 2024 Jan 01;221(1)

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    PMID: 38091025

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