In this study,we compared the serum levels of transforming growth factor-β1 (TGF-β1),interleukin-10 (IL-10),and arginase-1 in long-term survival kidney transplant recipients (LTSKTRs) with those in short-term survival kidney transplant recipients (STSKTRs).We then evaluated the relationship between these levels and graft function.Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs (graft survival approximately 1-3 years post-transplantation).All patients had stable kidney function.The samples were collected at our institution during the patients' follow-up examinations between March 2017 and September 2017.The plasma levels of TGF-β1,IL-10,and arginase-1 were analyzed using enzyme-linked immunosorbent assays (ELISA).The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs.The time elapsed since transplantation was positively correlated with the levels of TGF-β 1 and arginase-1 in the LTSKTRs.The estimated glomerular filtration rate was positively correlated with the TGF-β1 level,and the serum creatinine level was negatively correlated with the TGF-β1 level.Higher serum levels of TGF-β1 and arginase-1 were found in LTSKTRs than in STSKTRs,and we found that TGF-β1 was positively correlated with long-term graft survival and function.Additionally,TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation.On the basis of these findings,TGF-β1 and arginase-1 may play important roles in determining long-term graft survival.Thus,we propose that TGF-β1 and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival.

Recent data suggest that activation of aryl hydrocarbon receptor (AhR) by its high-affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in expansion of regulatory T (Treg) cells and suppresses the development of autoimmune and allergic diseases in several models. Treg cells have been increasingly documented to suppress allograft rejection and even to establish stable long-term graft acceptance. However, the involvement of TCDD in the regulation of solid organ transplantation rejection is largely unknown. Here, we examined whether activation of AhR with TCDD altered cardiac allograft rejection in an allogeneic heart transplant model. Recipient C57BL/6 (H-2b) mice were administrated with a single intraperitoneal injection of TCDD, and the murine cardiac transplant models from BALB/c (H-2d) to C57BL/6 (H-2b) were built 24 h later. The complete cessation of cardiac contractility was defined as the observation endpoint. The effect of TCDD on T-cell proliferation was assessed by mixed lymphocyte reaction (MLR). Histological and immunohistochemical analyses were performed to estimate the severity of rejection. The phenotype and cytokine profile of lymphocytes were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Activation of AhR remarkably prolonged the survival of cardiac allografts to more than 20 days. In vitro, TCDD ugregulated the frequency of CD4+CD25+Foxp3+ Treg cells and suppressed the proliferation of T lymphocytes. In vivo, the prolonged survival time was associated with increased number of Treg cells in allografts and spleens. Furthermore, the secretion of interferon-γ (IFN-γ) and interleukin-17 (IL-17) was reduced to less than 50% of that of the PBS treatment control group by TCDD treatment, whereas IL-10 was elevated to 10-fold of that of the PBS treatment control group. Collectively, our data indicate that activation of AhR with a single dose of TCDD significantly prolonged the survival of fully allogeneic cardiac grafts, and the mechanism underlying this effect might be involved in the induction of Treg cells.
Animals ; Graft Rejection ; immunology ; pathology ; prevention & control ; Graft Survival ; drug effects ; immunology ; Heart Transplantation ; adverse effects ; methods ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins ; pharmacology ; Receptors, Aryl Hydrocarbon ; immunology ; T-Lymphocytes ; immunology ; pathology ; T-Lymphocytes, Regulatory ; immunology ; pathology