Abstract：
:Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human TRM cells through study of donor-derived TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8+ TRM phenotypes. CD8+ CD69+CD103+ TRM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin+CD69+CD103- TRM cells have higher granzyme expression. Analysis of intestinal CD4+ T cells identifies several parallels, including a β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.
journal_name
Cell Repjournal_title
Cell reportsauthors
FitzPatrick MEB,Provine NM,Garner LC,Powell K,Amini A,Irwin SL,Ferry H,Ambrose T,Friend P,Vrakas G,Reddy S,Soilleux E,Klenerman P,Allan PJdoi
10.1016/j.celrep.2020.108661subject
Has Abstractpub_date
2021-01-19 00:00:00pages
108661issue
3issn
2211-1247pii
S2211-1247(20)31650-8journal_volume
34pub_type
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