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

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Abstract

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

Authors

Kai-C. Sonntag, David W. Emery, Akihiko Yasumoto, Gary Haller, Sharon Germana, Tomasz Sablinski, Akira Shimizu, Kazuhiko Yamada, Hideaki Shimada, Scott Arn, David H. Sachs, Christian LeGuern