Research Highlights and Editors’ Picks

Abstract

Recent years have witnessed remarkable expansion of the knowledge on reciprocal regulatory effect between various immune/inflammatory cells and T helper (Th) cell subsets including Th1, Th2, Th9, Th17, Th22, and follicular T-helper (Tfh) and regulatory T cells (Treg). Uncommitted naBve Th cells can be induced to differentiate to specific lineages according to the local cytokine milieu, towards Th or Treg phenotypes (1). The significance of Th17 immunity in acute, chronic and antibody-mediated allograft rejection is well known (2). However, Treg associated regulatory mechanisms have been implicated in tipping the balance in favor of tolerance rather than rejection (3). This review article summarizes the current knowledge on the contribution of T-helper subset cells in allograft rejection. The authors use a xenogeneic transplantation model to show the mechanisms by which Th1 cells participate in a allograft rejection. It also highlights that IL-12 or IFN-F knockout recipients showed faster acute vascular rejection than wildtype mice. Th2 cytokines inhibit Th1 responses and, as a result, can delay and even prevent acute rejection but seem to dominate during chronic rejection. The article also presents an extensive discussion of the involvement of Th17 in acute and chronic allograft rejection. The hallmark of Th17 cell-mediated allograft rejection is IL-17_s ability to recruit neutrophils which are one of the first inflammatory effector cells to infiltrate the allograft after transplantation and cause allograft damage. In addition a link between Th17 and alloimmunity particularly in the context of chronic lung allograft rejection is discussed. The final section of the review discusses the regulation of Th subsets by CD4+Foxp3+ Tregs in transplantation. It is well established that Tregs appear to be the Bmaster regulators[ that induce and maintain transplantation tolerance in experimental and clinical transplantation possibly by suppressing both Th1 and Th2 clones. Interestingly Th17 cells have the tendency to resist Treg-mediated suppression. The authors advocated that further studies are still needed to unravel the underlying mechanisms of these cells in the complex contexts of allograft rejection and tolerance and would facilitate devising strategies to achieve tolerance in the clinic.