Title | MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Andrlová H, Miltiadous O, Kousa AI, Dai A, DeWolf S, Violante S, Park H-Y, Janaki-Raman S, Gardner R, Daker SEl, Slingerland J, Giardina P, Clurman A, Gomes ALC, Nguyen C, da Silva MBurgos, Armijo GK, Lee N, Zappasodi R, Chaligne R, Masilionis I, Fontana E, Ponce D, Cho C, Bush A, Hill L, Chao N, Sung AD, Giralt S, Vidal EH, Hosszu KK, Devlin SM, Peled JU, Cross JR, Perales M-A, Godfrey DI, van den Brink MRM, Markey KA |
Journal | Sci Transl Med |
Volume | 14 |
Issue | 646 |
Pagination | eabj2829 |
Date Published | 2022 May 25 |
ISSN | 1946-6242 |
Keywords | Gastrointestinal Microbiome, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Ligands, Mucosal-Associated Invariant T Cells |
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. |
DOI | 10.1126/scitranslmed.abj2829 |
Alternate Journal | Sci Transl Med |
PubMed ID | 35613281 |
PubMed Central ID | PMC9893439 |
Grant List | P01 AG052359 / AG / NIA NIH HHS / United States T32 CA009512 / CA / NCI NIH HHS / United States P50 CA192937 / CA / NCI NIH HHS / United States P01 CA023766 / CA / NCI NIH HHS / United States R01 CA228308 / CA / NCI NIH HHS / United States R25 AI140472 / AI / NIAID NIH HHS / United States U01 AI124275 / AI / NIAID NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 CA228358 / CA / NCI NIH HHS / United States R01 HL125571 / HL / NHLBI NIH HHS / United States K08 HL143189 / HL / NHLBI NIH HHS / United States R01 HL123340 / HL / NHLBI NIH HHS / United States |