Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets

Journal article

Tissue-resident memory T (T_RM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal T_RM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human T_RM cells through study of donor-derived T_RM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8+ T_RM 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+ T_RM phenotypes. CD8+ CD69+CD103+ T_RM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin+CD69+CD103− T_RM 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+ T_RM cells.

Authors: FitzPatrick, MEB; Provine, NM; Garner, LC; Powell, K; Amini, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Reports
• Volume: 34
• Issue: 3
• Article number: 108661
• Publication date: 2021-01-19
• Acceptance date: 2020-12-22
• DOI: 10.1016/j.celrep.2020.108661
• ISSN: 2211-1247
• Pmid: 33472060
• Language: English
• Keywords: human; β2-integrin; CD103; T cell; residency; transplant; intestine; tissue resident; FFR; intestinal transplantation