The common γc-cytokines and transplantation tolerance

Transplant rejection, like tolerance, is a T cell-dependent event. There is compelling evidence to suggest that induction of transplant tolerance is an actively learned process in which T cells need to engage the alloantigens in order to learn to tolerate the allograft. A family of cytokines whose receptors use the same IL-2 receptor γ chain (also called the common γc) plays an important role in regulating multiple aspects of the allograft response (i.e. rejection vs. tolerance). It is undeniable that γc-cytokines can drive clonal expansion and effector maturation of alloreactive T cells, and therefore, targeting such cytokines or their receptor components remains an attractive way of blocking transplant rejection. However, we just started to appreciate that γc-cytokines also regulate the acquisition of transplant tolerance via programming activated T cells for apoptotic cell death and via guiding the evolution of regulatory T cells. Thus, understanding precisely the role of γc-cytokines in regulating T cell homeostasis and T cell regulation is critically important in the induction of transplant tolerance.