The Role of Costimulatory Pathways in Transplant Tolerance.

ABSTRACT

Costimulation is a critical step in T-cell activation, and costimulatory blockade at the time of T cell activation leads to T-cell anergy and allograft tolerance in animal models of transplantation. CD28B7 is the most important costimulatory pathway and the balance of signals between CD28 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a central determinant of transplant outcome. Form a clinical standpoint, CTLA-4 Ig is the only approved agent for costimulation blockade in transplantation. Advantages and disadvantages of its use are discussed. Progress in developing novel agents to target other pathways, including the promising CD40CD154 pathway, is also discussed.