MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT

MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT

MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT

Sci Transl Med . 2022 May 25;14(646):eabj2829.

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

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.