CD4+CD25+ regulatory T cells mediate acquired transplant tolerance.
The Holy Grail of clinical organ transplantation is the safe induction of allograft tolerance. Transplant tolerance has been successfully induced in animal models. Since T cells play a pivotal role in graft rejection, modulating T cell function has been the primary focus of studies aimed at inducing transplant tolerance. Rodent models of transplant tolerance induction include central deletion and peripheral mechanisms involving activation-induced cell death (AICD), anergy, immune deviation, and production of regulatory T cells. These mechanisms are not mutually exclusive. Although clonal deletion and anergy limit self-reactive T cells in the thymus, these mechanisms alone are not sufficient for controlling self-reactive T cells in the periphery. There is now evidence that the adult animal harbors two functionally distinct populations of CD4(+) T cells; one mediates autoimmune disease and the other dominantly inhibits it. The latter cells express CD4, CD25 and CTLA-4. These thymus-derived T cells have recently been shown to mediate the induction and maintenance of transplant tolerance. These CD4(+)CD25(+) T cells are similar in origin, phenotype, and function to those that maintain natural self-tolerance and T cell homeostasis in the periphery. Against this background, is it possible that alloantigen specific regulatory T cells might be generated and expanded ex vivo before organ transplantation and then infused to induce long-term tolerance, perhaps without the need for chronic immunosuppression?
Oluwole
Soji F
SF
Department of Surgery, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. so5@columbia.edu
Oluwole
Olakunle O
OO
DePaz
Hector A
HA
Adeyeri
Ayotunde O
AO
Witkowski
Piotr
P
Hardy
Mark A
MA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D023001:Transplantation Tolerance
D015375:Receptors, Interleukin-2