Tolerance to solid organ transplants through transfer of MHC class II genes
Kai-C. Sonntag, … , David H. Sachs, Christian LeGuern
Kai-C. Sonntag, … , David H. Sachs, Christian LeGuern
Published January 1, 2001
Citation Information: J Clin Invest. 2001;107(1):65-71. https://doi.org/10.1172/JCI11015.
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Article

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

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

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Figure 1

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PCR analysis of MHC class II DRB and DQB transgenes. (a) Results from a ...
PCR analysis of MHC class II DRB and DQB transgenes. (a) Results from a representative long-term graft–accepting animal, no. 11585 (DRB, top), and a tolerant animal, no. 12307 (DQA+B, bottom). WBC and BM samples, taken at various time points after BMT, were analyzed for actin and retroviral DRB or DQB cDNA. Specific PCR products for actin (414 bp), DRB (358 bp), and DQB (461 bp) are shown. GS4.5-16 and STP29.20 are DRB- and DQA+B-virus producing cell clones, respectively. (b) RT-PCR and DNA-PCR analyses performed on WBC and BM samples from long-term graft–accepting pigs. Filled, gray, and open bars indicate the presence of DRB or DQB Tg DNA, DRB or DQB Tg transcription, and graft survival, respectively. KTx was performed at times indicated by arrows. Numbers over brackets show graft persistence (in days) following cessation of Tg transcription.