CD40-ligand in primate cardiac allograft and viral immunity

Our laboratory has studied the role of CD40 ligand (CD40L, CD154) in the pr imate immune response to allogenic and infectious challenges. We find that intensive early blockade of CD40L reliably attenuates acute rejection of pr imate cardiac allografts. Monotherapy fails to prevent late graft loss, whi ch often occurs in association with rising antidonor antibody titers and al lograft vasculopathy, despite continuing anti-CD40L therapy. In contrast, t he primary humoral response to T helper dependent influenza viral antigen i s inhibited during anti-CD40L therapy, and responses to subsequent immuniza tion are blunted after discontinuation of therapy. These results are encour aging with regard to the tolerogenic potential of costimulatory blockade fo r specific T helper dependent antigens. However, these findings also indica te that pathogenic allograft responses in primates are probably not entirel y CD40L-dependent. As such, additional immunomodulatory strategies are need ed to facilitate tolerance to a transplanted organ.