Regulatory T cells under scrutiny

Abstract

Purpose of review There is increasing evidence that regulatory T cells play a central role in the control of both reactivity to self-antigens and alloimmune response. This review focuses on the importance of regulatory T cells in clinical transplantation as a marker of hyporesponsiveness against donor antigens and as a potential therapeutic tool for tolerance induction. Recent findings Several subsets of regulatory T cells with distinct phenotypes and mechanisms of action have now been identified. They constitute a network of heterogeneous CD4+ or CD8+ T cell subsets and other minor T-cell populations with mechanisms of action that can be cell-contact dependent or independent. Considerable progress has been made in characterization of regulatory T cells, such as identification of FoxP3 as a specific marker. Regulatory T cells not only play a main role in maintaining self tolerance and preventing autoimmune disease, but can also be induced by tolerance protocols and seem to play a key role in preventing allograft rejection, as demonstrated in many animal models. Of particular interest, in stable transplant patients CD4+CD25+ and CD8+CD28− regulatory T cells have been recently shown to modulate immune response toward donor antigens in the indirect and direct pathway, respectively. This finding raises the possibility that such regulatory T cells also have a role in induction or maintenance of transplant tolerance in humans. Summary Regulatory T cells have been shown to be an essential tool by which the immune system can actively control immune responses. Future developments of transplantation research would probably have regulatory T cells as protagonists for immunologic monitoring as well as for induction of transplant tolerance.