Role and mechanisms of CD4⁺CD25⁺ regulatory T cells in the induction and maintenance of transplantation tolerance

To gain transplantation tolerance between donor organs and hosts is the ultimate goal of all sorts of organ transplantations. Induction of regulatory T cells has been demonstrated to lead to transplantation tolerance. This paper will review subsets of regulatory T cells, the role and mechanisms of CD4⁺CD25⁺ regulatory T cells (Tregs) in graft rejection and tolerance, pathway used by Tregs to recognized alloantigens, pathways of Tregs homing into the graft and effects of immunosuppression on Tregs. It was well known that Tregs play a pivotal role in transplantation tolerance. The mechanisms by which Tregs exert their regulatory effect in the induction and maintenance of transplantation tolerance, anthropogenicly, consist of physical cell-to-cell contact with potential target cells, autocrine and paracrine properties. ICAM-1, TGF-beta, CTLA-4, GITR and OX40 (CD134), etc. are involved in the regulatory function of Tregs through cell-to-cell contact mechanism. IL-10 and TGF-βare two important soluble mediators involved in the autocrine mechanism by which Tregs exert their regulatory function. Paracrine properties refer to reeducate potentially destructive alloresponsive T cells to gain regulatory function. All that discussed above could illustrate, at least partially, how naturally occurring Tregs exert their regulatory function in vivo as they constitute only 5-10% of peripheral CD4⁺ T cells.