Novel roles of OX40 in the allograft response.
OBJECTIVE
In the past few years, much effort has been focused on the identification of new pathways, new mechanisms, and new therapeutic targets in transplant models. Understanding of T-cell costimulatory molecules remains one of the highly contested areas of research. In this review, we will focus specifically on OX40, and summarize the latest developments on the role of OX40 in transplant models.


RESULTS
OX40 regulates multiple aspects of the T-cell response; it delivers a potent costimulatory signal to T effector cells and plays a key role in their survival and proliferation. OX40 also supports the transition of activated T effector cells to memory T cells. Importantly, OX40 signaling inhibits the suppressor functions of forkhead box P3 T regulatory cells and also blocks the induction of new forkhead box P3 T regulatory cells from activated T effector cells. These new findings may have major clinical implications in the induction of transplant tolerance.


CONCLUSIONS
The current belief is that tolerance to organ transplants involves the apoptotic deletion of T effector cells and the expansion of graft-protective T regulatory cells. Given our recent understanding of OX40, we believe that targeting the OX40 costimulation is therapeutically important in the induction of transplant tolerance.
Demirci
Gulcin
G
Transplant Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Li
Xian Chang
XC
D000818:Animals; D008213:Lymphocyte Activation; D053262:Receptors, OX40 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology; D023001:Transplantation Tolerance
D053262:Receptors, OX40