A Reproducible Pre-Transplant γδ T-cell Effector Signature Reveals Immune-Metabolic Programs Associated with Kidney Allograft Rejection

A reproducible pre-transplant depletion of {gamma}{delta} T cells is linked to kidney allograft rejection, with a higher {beta}/{gamma}{delta} ratio and an AUC up to 0.71.

• Why it matters: Acute rejection still occurs in 10–20% of kidney transplant recipients within a year, and there is no reliable pre-transplant molecular test independent of donor HLA matching.
• What they did: Across three independent recipient cohorts, bulk RNA-seq with T-cell receptor repertoire analysis, flow cytometry, and CyTOF with paired metabolomics were used to track {gamma}{delta} T-cell effector clusters and metabolomic programs over time.
• The result: In a longitudinal cohort, {gamma}{delta} T-cell depletion was present at pre-transplant baseline in future rejectors and persisted, while marker expression predicted rejection risk (AUC = 0.69) and improved marginally with metabolomic integration (AUC = 0.71).

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