Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization.

ABSTRACT: Sensitization is a critical unresolved challenge in transplantation. We show for the first time that blockade of CD154 alone or combined with T-cell depletion prevents sensitization. Allogeneic skin grafts were rejected by recipients treated with anti-alphabeta T-cell receptor (TCR), anti-CD154, anti-OX40L, or anti-inducible costimulatory pathway (ICOS) mAb alone with a kinetic similar to untreated recipients. However, the production of anti-donor MHC antibody was prevented in mice treated with anti-CD154 mAb only, suggesting a specific role for the CD154-CD40 pathway in B-cell activation. The impairment of T cell-dependent B-cell responses by blocking CD154 occurs through inhibiting activation of T and B cells and secretion of IFN-gamma and IL-10. Combined treatment with both anti-CD154 a

SUBMITTER: Xu H 

PROVIDER: S-EPMC2265462 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature