Background and Objectives:Inflammatory interstitial fibrosis and tubular atrophy (i-IFTA) is an inflammation in the area of tubular atrophy and fibrosis. i-IFTA is poorly associated with graft outcome and associated with infiltration of inflammatory mononuclear cells. A cytotoxic T cell is a granzyme B+CD8+CD3+T cell, mainly secret granzyme B. Granzyme B is a serine protease that may mediate allograft injury and inflammatory interstitial fibrosis and tubular atrophy (i-IFTA). However, there is no report identifying the association of granzyme B with i-IFTA after a long post-transplant interval.Material and Methods:In this study, we have measured the cytotoxic T-cell frequency with flow cytometry, serum and PBMCs culture supernatants granzyme-B levels with ELISA and intragraft granzyme-B mRNA transcript expression with the RT-PCR in RTRs in 30 patients with biopsy-proven i-IFTA and 10 patients with stable graft function.Result:The frequency of cytotoxic T cells (CD3+CD8+granzyme B+) in SGF vs. i-IFTA was (27.96 ± 4.86 vs. 23.19 ± 3.85%,p= 0.011), the serum granzyme-B level was (100.82 ± 22.41 vs. 130.32 ± 46.60,p= 0.038 pg/mL) and the intragraft granzyme-B mRNA transcript expression was (1.01 ± 0.048 vs. 2.10 ± 1.02,p< 0.001 fold). The frequency of CD3+T cells in SGF vs. i-IFTA was (66.08 ± 6.8 vs. 65.18 ± 9.35%;p= 0.68) and that of CD3+CD8+T cells was (37.29 ± 4.11 vs. 34.68 ± 5.43%;p= 0.28), which were similar between the 2 groups. CTLc frequency was negatively correlated with urine proteinuria (r = −0.51,p< 0.001), serum creatinine (r = −0.28,p= 0.007) and eGFR (r = −0.28,p= 0.037). Similarly, the PBMC culture supernatants granzyme-B level was negatively correlated with urine proteinuria (r = −0.37,p< 0.001) and serum creatinine (r = −0.31,p= 0.002), while the serum granzyme-B level (r = 0.343,p= 0.001) and intragraft granzyme-B mRNA transcript expression (r = 0.38,p< 0.001) were positively correlated with proteinuria.Conclusions:A decrease in the CTLc frequency in circulation and an increased serum granzyme-B level and intragraft granzyme-B mRNA expression shows that cytotoxic T cells may mediate the allograft injury in RTRs with i-IFTA by releasing granzyme B in serum and intragraft tissue.