Regulatory T Cells in the Immunodiagnosis and Outcome of Kidney Allograft Rejection

Abstract

Acute rejection (AR) is responsible for up to 12% of graft loss with the highest risk generally occurring during the first six months after transplantation. AR may be broadly classified into humoral as well as cellular rejection. Cellular rejection develops when donor alloantigens, presented by antigen-presenting cells (APCs) through class I or class II HLA molecules, activate the immune response against the allograft, resulting in activation of naive T cells that differentiate into subsets including cytotoxic CD8+ and helper CD4+ T cells type 1 (TH1) and TH2 cells or into cytoprotective immunoregulatory T cells (Tregs). The immune reaction directed against a renal allograft has been suggested to be characterized by two major components: a destructive one, mediated by CD4+ helper and CD8+ cytotoxic T cells, and a protective response, mediated by Tregs. The balance between these two opposite immune responses can significantly affect the graft survival. Many studies have been performed in order to define the role of Tregs either in the immunodiagnosis of transplant rejection or as predictor of the clinical outcome. However, information available from the literature shows a contradictory picture that deserves further investigation.

A Critical Review of Steroid Immunotherapy in Kidney Transplantation

“…Glucocorticoid treatment tilts the balance in favor of grafttolerance by promoting the regulatory [Foxp3+ CD4+ CD25+] T-cells while inhibiting the cytotoxicity of T-effector cells [65,66]. Similarly, compared with the staining for IL-17 cytokines, individuals with renal histological specimen that expresses FOXP3 had lower frequency of steroid-resistant rejection events [66,67].…”

“…Glucocorticoid treatment tilts the balance in favor of grafttolerance by promoting the regulatory [Foxp3+ CD4+ CD25+] T-cells while inhibiting the cytotoxicity of T-effector cells [65,66]. Similarly, compared with the staining for IL-17 cytokines, individuals with renal histological specimen that expresses FOXP3 had lower frequency of steroid-resistant rejection events [66,67]. In addition, maintenance dose of steroids after a successful treatment of an acute rejection with pulse GC therapy results in a lower occurrence of a Inside the cell, maximum interaction with cytosolic glucocorticoid receptor (GR) occurs with the binding to a complex of chaperones that include immunophilin binding protein (FK506-BP) and heat shock proteins (HSP).…”

Updates on acute and chronic rejection in small bowel and multivisceral allografts

“…However, vasculitis is not specific to antibodies, as T-cell-mediated immunity can also be an underlying cause of this lesion in bowel allograft vessels. This rejection is the result of effectorimmune T-cell populations being in greater scale and function than the regulatory T-cell populations [46] that suppress ACR. Larger vessel vasculitis is typically identified in explants or rejected organs or autopsies.…”

Analysis of regulatory T cell subsets in the peripheral blood of immunoglobulin A nephropathy (IgAN) patients

“…Regulatory T cells (Treg) are involved in inhibiting T cell activation and in developing immune tolerance against autoimmune diseases, tumors, and allografts (Whibley and Gaffen, 2014;Kumar and Subramaniyam, 2015). T helper 17 and Treg cells mutually restrict each other in the body, which helps maintain immune homeostasis (Franzese et al, 2013;Shan et al, 2015). Previous studies have shown that Tregs level was reduced in IgAN patients, which lead to their weakened ability to suppress immune responses.…”