Tolerogenic antibodies and fusion proteins to prevent graft rejection and treat autoimmunity.

The immune mechanisms underlying autoimmune diseases and allograft rejection are similar, and T cells play a major role in both processes. Current therapeutic strategies rely on the application of nonspecific immunosuppression using chemicals such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporin. One major drawback of these drugs is their relative ineffectiveness over the long term; withdrawal leads to recurrence of the disease, but chronic administration puts patients at risk of being overimmunosuppressed, which can result in an increased incidence of infections and tumors. This review describes the advantages of developing biological agents that target immune receptors on T cells. In some cases, these agents can induce a state of durable, antigen-specific unresponsiveness in the absence of generalized immunosuppression, which could be useful in transplantation and autoimmunity.