Immune features of graft‐derived mucosal‐associated invariant T cells predict gastrointestinal graft‐versus‐host disease

Abstract

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.