Immune features of graft-derived mucosal-associated invariant T cells predict gastrointestinal graft-versus-host disease.
Gastrointestinal acute graft-versus-host disease (GI aGVHD) remains a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), and early risk identification and intervention are essential for improving outcomes. Mucosal-associated invariant T (MAIT) cells are mucosa-enriched unconventional T cells with major histocompatibility complex class I-related protein 1 (MR1)-restricted, major histocompatibility complex (MHC)-independent recognition, suggesting a potentially reduced risk of alloreactivity. Our previous work showed that higher graft MAIT-cell levels were associated with improved post-transplant MAIT-cell reconstitution and a lower incidence of GI aGVHD. Single-cell ribonucleic acid (RNA) sequencing (sc-RNA-seq) and murine models revealed their functional heterogeneity in immune regulation, tissue repair and chemotaxis-supporting their role as both biomarkers and therapeutic targets. In this prospective study, spectral flow cytometry was used to characterize MAIT-cell phenotypes in peripheral blood stem cell grafts. higher graft MAIT-cell abundance was associated with more robust early post-transplant MAIT-cell reconstitution and a lower risk of GI aGVHD. A three-marker predictive panel based on MAIT-cell functional markers (C-C chemokine receptor type 2 [CCR2], interleukin-4 [IL-4], interleukin-17A [IL-17A]) achieved an area under the receiver operating characteristic curve (AUC) of 0.80, increasing to 0.85 after adjustment for clinical covariates. These findings identify graft-derived MAIT cells as a predictive immune-associated biomarker for GI aGVHD, enabling pre-transplant risk stratification and supporting precision prevention strategies. Trial registration: ChiCTR2500095349.