Interruption of OX40L signaling prevents costimulation blockade-resistant allograft rejection.

ABSTRACT: The potential of costimulation blockade to serve as a novel transplant immunosuppression strategy has been explored for over 20 years, culminating in the recent clinical approval of belatacept for renal transplant patients. Despite improving long-term graft function and survival compared with calcineurin inhibitors, clinical acceptance of belatacept has been hindered by elevated rates of acute rejection. We examined the signaling pathways required to activate costimulation blockade-resistant alloreactive T cells and identified the OX40/OX40L secondary costimulatory pathway as a promising target. We next sought to improve the clinical efficacy of traditional costimulation blockade using belatacept by coupling it with anti-OX40L. Using a murine transplant model, we demonstrate that combined

SUBMITTER: Kitchens WH 

PROVIDER: S-EPMC5333968 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature