Mechanisms underlying the development of T-cell tolerance following interruption of signalling at the CD28/B7 and CD40/gp39 interface.

WE HAVE SHOWN previously that combined but not discrete transient perioperative blockade of CD28!B7 and CD40/gp39 costimulatory pathways results in indefinite prolongation of islet allograft survival.! Similar observations have also been made in the realm of solid organ transplantation (TX).2 Additionally, the use of both rhCTLA4-Ig and anti-gp39 mAb (but not alone) have also resulted in abrogation of morphologic changes considered pathognomonic of posttransplant vasculopathy.3 Although the profound immunosuppressive effects of contemporaneous blockade of both costimulatory pathways have been established, not evident, however, are the underlying cellular mechanism(s) responsible for the observed outcome. The present study was therefore designed to address the latter issue.