Tolerance to solid organ transplants through transfer of MHC class II genes

Donor/recipient MHC class II. matching permits survival of experimental all ografts without permanent immunosuppression, but is not clinically applicab le due to the extensive polymorphism of this locus. As an alternative, we h ave tested a gene therapy approach in a preclinical animal model to determi ne whether expression of allogeneic class II transgenes (Tg's) in recipient bone marrow cells would allow survival of subsequent Tg-matched renal allo grafts. Somatic matching between donor kidney class II and the recipient Tg 's, in combination with a short treatment of cyclosporine A, prolonged graf t survival with DR and promoted tolerance with DQ. Class II Tg expression i n the lymphoid lineage and the graft itself were sequentially implicated in this tolerance induction. These results demonstrate the potential of MHC c lass II gene transfer to permit tolerance to solid organ allografts.