The common gammac-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 gamma chain (also called the common gammac) plays an important role in regulating multiple aspects of the allograft response (i.e. rejection vs. tolerance). It is undeniable that gammac-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 gammac-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 gammac-cytokines in regulating T cell homeostasis and T cell regulation is critically important in the induction of transplant tolerance.
Vu
Minh Diem
MD
Department of Medicine, Harvard Medical School, Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Li
Xian Chang
XC
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000737:chemistry*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
D016207:Cytokines; D015375:Receptors, Interleukin-2