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  • MAIT and Vδ2 unconventional...
    Andrlová, Hana; Miltiadous, Oriana; Kousa, Anastasia I; Dai, Anqi; DeWolf, Susan; Violante, Sara; Park, Hee-Yon; Janaki-Raman, Sudha; Gardner, Rui; El Daker, Sary; Slingerland, John; Giardina, Paul; Clurman, Annelie; Gomes, Antonio L C; Nguyen, Chi; da Silva, Marina Burgos; Armijo, Gabriel K; Lee, Nicole; Zappasodi, Roberta; Chaligne, Ronan; Masilionis, Ignas; Fontana, Emily; Ponce, Doris; Cho, Christina; Bush, Amy; Hill, Lauren; Chao, Nelson; Sung, Anthony D; Giralt, Sergio; Vidal, Esther H; Hosszu, Kinga K; Devlin, Sean M; Peled, Jonathan U; Cross, Justin R; Perales, Miguel-Angel; Godfrey, Dale I; van den Brink, Marcel R M; Markey, Kate A

    Science translational medicine, 05/2022, Letnik: 14, Številka: 646
    Journal Article

    Microbial diversity is associated with improved outcomes in recipients of allogeneic hematopoietic cell transplantation (allo-HCT), but the mechanism underlying this observation is unclear. In a cohort of 174 patients who underwent allo-HCT, we demonstrate that a diverse intestinal microbiome early after allo-HCT is associated with an increased number of innate-like mucosal-associated invariant T (MAIT) cells, which are in turn associated with improved overall survival and less acute graft-versus-host disease (aGVHD). Immune profiling of conventional and unconventional immune cell subsets revealed that the prevalence of Vδ2 cells, the major circulating subpopulation of γδ T cells, closely correlated with the frequency of MAIT cells and was associated with less aGVHD. Analysis of these populations using both single-cell transcriptomics and flow cytometry suggested a shift toward activated phenotypes and a gain of cytotoxic and effector functions after transplantation. A diverse intestinal microbiome with the capacity to produce activating ligands for MAIT and Vδ2 cells appeared to be necessary for the maintenance of these populations after allo-HCT. These data suggest an immunological link between intestinal microbial diversity, microbe-derived ligands, and maintenance of unconventional T cells.