Alternative T-Cell Costimulatory Pathways in Transplant Rejection and Tolerance Induction: Hierarchy or Redundancy?

Since the original proposal of a two-signal model for lymphocyte activation (1), it has become firmly established that costimulatory signals mediated primarily via the conventional CD28-B7 and CD154-CD40 pathways, are necessary for full T-cell activation and play a crucial role in mediating allograft rejection (2). In several transplantation models, CD28-B7 or CD154-CD40 blockade has been shown to prevent acute rejection, induce long-term allograft survival and prevent the development and progression of chronic rejection.