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Article

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

by
Petar Đolonga
1,2,
Petar Šenjug
3,4,
Anja Stadnik
3,
Ana Dunatov Huljev
1,2,
Lada Zibar
5,6,
Sandra Zekić Tomaš
1,2,
Danica Galešić Ljubanović
3,4,7 and
Merica Glavina Durdov
1,2,*
1
Department of Pathology, Judicial Medicine, and Cytology, University Hospital of Split, Spinčićeva 1, 21000 Split, Croatia
2
Department of Pathology, University of Split School of Medicine, Šoltanska 2, 21000 Split, Croatia
3
Department of Nephropathology and Electron Microscopy, Dubrava University Hospital, Avenija Gojka Šuska 6, 10000 Zagreb, Croatia
4
Institute of Pathology, School of Medicine, University of Zagreb, Šalata 10, 10000 Zagreb, Croatia
5
Department of Nephrology, Clinical Hospital Merkur, Zajčeva 19, 10000 Zagreb, Croatia
6
Department of Pathophysiology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Huttlerova 4, 31000 Osijek, Croatia
7
Faculty of Farmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Medicina 2026, 62(9), 1746; https://doi.org/10.3390/medicina62091746
Submission received: 10 July 2026 / Revised: 1 September 2026 / Accepted: 8 September 2026 / Published: 10 September 2026
(This article belongs to the Section Urology & Nephrology)

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.
Keywords: T cell-mediated rejection; kidney allograft; Banff classification; FOXP3 T cell-mediated rejection; kidney allograft; Banff classification; FOXP3

Share and Cite

MDPI and ACS Style

Đolonga, P.; Šenjug, P.; Stadnik, A.; Dunatov Huljev, A.; Zibar, L.; Zekić Tomaš, S.; Galešić Ljubanović, D.; Glavina Durdov, M. Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection. Medicina 2026, 62, 1746. https://doi.org/10.3390/medicina62091746

AMA Style

Đolonga P, Šenjug P, Stadnik A, Dunatov Huljev A, Zibar L, Zekić Tomaš S, Galešić Ljubanović D, Glavina Durdov M. Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection. Medicina. 2026; 62(9):1746. https://doi.org/10.3390/medicina62091746

Chicago/Turabian Style

Đolonga, Petar, Petar Šenjug, Anja Stadnik, Ana Dunatov Huljev, Lada Zibar, Sandra Zekić Tomaš, Danica Galešić Ljubanović, and Merica Glavina Durdov. 2026. "Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection" Medicina 62, no. 9: 1746. https://doi.org/10.3390/medicina62091746

APA Style

Đolonga, P., Šenjug, P., Stadnik, A., Dunatov Huljev, A., Zibar, L., Zekić Tomaš, S., Galešić Ljubanović, D., & Glavina Durdov, M. (2026). Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection. Medicina, 62(9), 1746. https://doi.org/10.3390/medicina62091746

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