The imbalance between Tregs, Th17 cells and inflammatory cytokines among renal transplant recipients

Abstract

Background: A significant barrier to organ transplantation is the cellular rejection that occurs and mediated by antibodies, T cells, and innate immune cells. This study was aimed to determine the number of CD4+CD25+Foxp3+ Treg, CD4+IFN-γ-IL-17+ Th17, CD4+IFN-γ+IL-17- Th1 and CD4+IFN-γ+IL-17+ Th1/17 cells in renal transplant recipients (RTR). Methods: Renal transplantation was performed for a total of 35 patients with end-stage renal failure. The number of CD4+CD25+Foxp3+ Treg, CD4+IFN-γ-IL-17+ Th17, CD4+IFN-γ+IL-17- Th1 and CD4+IFN-γ+IL-17+ Th1/17 cells, and the serum level of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17 were measured in pre- and post-transplant patients and 10 healthy controls (HC) using flow cytometry and Cytometric Bead Array (CBA). The association between the number of different subsets of CD4+ T-cells and clinical parameters were analyzed among the pre- and post-transplant patients, and the healthy controls. Results: The number of CD4+IFN-γ-IL-17+ Th17, CD4+IFN-γ+IL-17- Th1 and CD4+IFN-γ+IL-17+ Th1/17 cells were significantly increased in patients with End-Stage Renal Failure (ESRF) compared to the HC. Stratification analysis indicated that AMR (Acute antibody mediated acute rejection), AR (acute rejection) and CR (chronic rejection) groups displayed greater number of CD4+IFN-γ-IL-17+ Th17, CD4+IFN-γ+IL-17- Th1 and CD4+IFN-γ+IL-17+ Th1/17 cells as well as high level of serum IL-2, IFN-γ, TNF-α and IL-17. But, the AMR, AR and CR groups have shown lower level of CD4+CD25+Foxp3+ T cells and serum IL-10 compared to transplant stable (TS) patients. Moreover, the number of Tregs were negatively correlated with the number of Th17 cells in RTR patients. The number of Tregs and Th17 cells were positively correlated with the eGFR and serum creatinine values, respectively. Conclusion: The imbalance between different types of CD4+ T cells and dysregulated inflammatory cytokines may contribute towards renal transplantation rejection.