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

H Andrlová, O Miltiadous, AI Kousa, A Dai… - Science translational …, 2022 - science.org
H Andrlová, O Miltiadous, AI Kousa, A Dai, S DeWolf, S Violante, HY Park, S Janaki-Raman
Science translational medicine, 2022science.org
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 …
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.
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