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

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 ChaligneIgnas 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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Article numbereabj2829
JournalScience Translational Medicine
Volume14
Issue number646
DOIs
StatePublished - 25 May 2022
Externally publishedYes

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