Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection

Abstract

Background and Objectives: FOXP3+ (Forkhead box P3) regulatory T cells contribute to immune tolerance after kidney transplantation, but their role in T cell-mediated rejection (TCMR) remains controversial. This study investigated the association between intragraft FOXP3+ cells and the recently introduced Banff-derived activity (AI) and chronicity index (CI) in biopsy-proven TCMR. Materials and Methods: This retrospective cross-sectional study included 119 kidney allograft biopsies diagnosed as acute or chronic active TCMR according to the Banff classification. FOXP3+ cells were assessed by immunohistochemistry and expressed as cortical cell density (cells/mm2). Associations between FOXP3+ cell density, Banff-derived indices, inflammatory cell densities, and clinical parameters were analyzed using non-parametric statistical methods. Results: FOXP3+ cells were detected in 17.6% of biopsies. FOXP3+ cell density was univariately associated with higher CI values (ρ = 0.228, p = 0.013) and chronic lesions interstitial fibrosis (ci) (ρ = 0.284, p = 0.002) and tubular atrophy (ct) (ρ = 0.246, p = 0.008). No association was observed with AI or activity lesions, except for a weak negative correlation with interstitial inflammation (i) (ρ = −0.209, p = 0.025). In multivariable analysis, FOXP3 positivity was not significantly associated with CI after adjustment for transplantation–biopsy interval (B = 0.568, 95% CI −0.741–1.876, p = 0.391). FOXP3+ cell density positively correlated with cluster of diferentiation (CD)4+ (ρ = 0.350, p < 0.001), CD8+ (ρ = 0.229, p = 0.018), and CD163+ (ρ = 0.207, p = 0.047) cell densities. No association with short-term graft outcome was observed. Conclusions: FOXP3+ cell infiltration was associated with chronic histological changes in unadjusted analyses, but this association did not remain statistically significant after adjustment for transplantation-to-biopsy interval. These preliminary findings suggest that FOXP3+ cell accumulation and chronic histological changes may represent parallel time-dependent phenomena and require confirmation in larger cohorts.