Unsupervised Immune Profiling Identifies Distinct Post-Transplant T-Cell Clusters Associated with Kidney Allograft...

Post-transplant immune heterogeneity may influence kidney allograft outcomes, yet the clinical relevance of circulating T-cell phenotypes remains incompletely defined. We aimed to identify 12-month post-transplant data-driven T-cell clusters and examine their relation to graft-function patterns during the first post-transplant year.

Peripheral blood T-cell subpopulations were analyzed in 112 kidney transplant recipients at 12 months post-transplantation using flow cytometry. Standardized subpopulation frequencies underwent unsupervised hierarchical clustering, with principal component analysis used for visualization. Longitudinal graft function trajectories (eGFR and serum creatinine at 1, 3, 6, and 12 months) were analyzed using generalized estimating equation models, including time-by-cluster interactions.

Three recipient clusters were identified: a CD8-skewed cytotoxic/senescent cluster, an innate-like cytotoxic cluster, and a CD4-dominant cluster. Cluster robustness was supported by complementary k-means analysis. Older recipient age and baseline cytomegalovirus seropositivity were associated with the CD8-skewed cluster. Recipients assigned to different T12 clusters showed differences in serum creatinine levels and graft function trajectories, although some associations were attenuated after additional adjustment for transplant-related factors.

In this cohort, unsupervised clustering identified distinct post-transplant T-cell profiles associated with early graft function patterns. These findings are hypothesis-generating and require longitudinal and external validation.