Resident memory CD8 T cells persist for years in human small intestine
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Resident memory CD8 T cells (Trm) have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for over 1 year in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine-producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.
Study Datasets 2 datasets.
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5000 cells of each subset of CD8 T cells (CD103-KLRG1+, CD103-KLRG1- and CD103+ from LP and CD103+ IELs) were sorted into tubes. A modified SMART protocol was used in first-strand cDNA synthesis, and TCRalpha / TCRbeta genes were amplified in two rounds of semi-nested PCR reaction, following the method described in detail in Risnes et al., 2018.
Single-cell TCRalpha-beta sequencing of LP CD103+ CD8 T cells from the grafted/native duodenum of two donors (Ptx#1 and Ptx#2) before and 1 year after transplantation. Single cells were sorted into 96-well plates. Paired TCRalpha and TCRbeta sequences were obtained after three nested PCR with multiplexed primers covering all TCRalpha and TCRbeta V genes, as described before (Risnes et al., 2018), and original protocol in (Han et al., 2014).
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