Transplantation is the treatment of choice for patients with end-stage organ failure. Its success is limited by side effects of immunosuppressive drugs, such as inhibitors of the calcineurin pathway that prevent rejection by reducing synthesis of interleukin-2 by T cells. Moreover, none of the existing drugs efficiently prevent the late development of chronic rejection. Blocking the CD28-mediated T cell costimulation pathway is a non toxic alternative immunosuppression strategy that is currently achieved by blockade of CD80/86, the counter receptors for CD28 on antigenpresenting cells.. However interaction of CD80/86 with CTLA-4 is required for immune regulation. Therefore CD28 blockade, instead of CD80/86 blockade, might preserve regulatory signals mediated by CTLA-4 and favor immune regulation. By using monovalent antibodies, we identified true CD28 antagonists inducing a CTLA-4-dependent decreased T cell function compatible with regulatory T cell (Treg) suppression. In transplantation experiments in primates, blocking CD28 augmented intragraft and peripheral blood regulatory T cells, induced molecular signatures of immune regulation and prevented graft rejection and vasculopathy in synergy with calcineurin inhibition. These findings suggest that targeting costimulation blockade at CD28 favors CTLA-4-dependent immune regulation and promotes allograft survival.
Childhood-onset AAV is a rare disease characterized by female predominance, delayed diagnosis, frequent renal impairment and a high remission rate. Baseline GFR and new histopathological classification system are strong predictors of ESRD. Renal survival in childhood AAV has improved over time.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.