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<jats:title>Abstract</jats:title><jats:p>Tissue-resident memory T (T<jats:sub>RM</jats:sub>) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal T<jats:sub>RM</jats:sub> cells remains undefined, and definitive markers of CD103-T<jats:sub>RM</jats:sub> cells are lacking. Here, we investigated transcriptional and functional heterogeneity of human T<jats:sub>RM</jats:sub> cells through the study of donor-derived intestinal T<jats:sub>RM</jats:sub> cells from intestinal transplant recipients. Single-cell transcriptional profiling identified four conventional T<jats:sub>RM</jats:sub> populations, with two distinct transcriptional states of CD8+ T<jats:sub>RM</jats:sub> cells, delineated by <jats:italic>ITGAE</jats:italic> and <jats:italic>ITGB2</jats:italic> expression. We defined a transcriptional signature discriminating the two CD8+ populations, including differential expression of key residency-associated genes and cytotoxic molecules. Flow cytometry of recipient-derived cells infiltrating the graft and intestinal lymphocytes from healthy gut confirmed the two CD8+ T<jats:sub>RM</jats:sub> phenotypes, with β2-integrin acting as a CD103-CD8+ T<jats:sub>RM</jats:sub> marker. CD103+ CD8+ T<jats:sub>RM</jats:sub> cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103-T<jats:sub>RM</jats:sub> cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal T<jats:sub>RM</jats:sub> cells, and suggest a role for β2-integrin in T<jats:sub>RM</jats:sub> development.</jats:p><jats:sec><jats:title>Summary</jats:title><jats:p>Heterogeneity within human tissue-resident memory T (T<jats:sub>RM</jats:sub>) cells is poorly understood. We show that transcriptionally, phenotypically, and functionally distinct CD4+ and CD8+ T<jats:sub>RM</jats:sub> subsets exist in the human intestine, and that β2-integrin expression identifies a distinct population of CD8+ T<jats:sub>RM</jats:sub> cells.</jats:p></jats:sec>

Original publication

DOI

10.1101/869917

Type

Journal article

Publisher

Cold Spring Harbor Laboratory

Publication Date

12/12/2019