Conventional immunosuppression and co-stimulation blockade

Organ transplantation has become an accepted and successful therapeutic int ervention for marry patients with end-stage organ disease. Current conventi onal immunosuppressive regimens achieve very good short-term allograft surv ival but long-term outcomes are less than adequate. Furthermore, non-specif ic immunosuppression has its attendant side-effects including increased ris ks of malignancy and infection as well as drug-specific sequellae. With rec ent advances in the field of immunology promising new therapies have arisen that could potentially eliminate lifelong drug therapy and promote indefin ite acceptance of the donor tissue. Identification of co-stimulatory signal s essential for T-c-ell activation has provided exciting neu possibilities for controlling tile alloimmune response. The compatibility of these new ag ents with proven conventional therapeutics has yielded mixed results. When used in combination, their immunosuppressive e properties appear synergisti c. However, if the goal of therapy) is sustained, specific T-cell hyporespo nsiveness, many conventional agents antagonize the effects of co-stimulator y blockade in several immune tolerance models.