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Science 21 June 1991:
Vol. 252. no. 5013, pp. 1700 - 1702
DOI: 10.1126/science.1710828
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Articles

Science, Vol 252, Issue 5013, 1700-1702
Copyright © 1991 by American Association for the Advancement of Science

articles

Prevention of xenograft rejection by masking donor HLA class I antigens

D Faustman and C Coe

Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02129.

Destruction of target cells by cytotoxic T lymphocytes requires the presence of HLA (human lymphocyte antigen) class I antigens on the target cells for adhesion as well as for triggering of the antigen-specific T cell receptor. Rejection of xenogeneic human pancreatic islets and liver was circumvented by masking, before transplantation, donor antigens with F(ab')2 antibody fragments to HLA class I or tissue-specific epitopes. This strategy eliminated the need for recipient immunosuppression and allowed islet xenograft survival beyond 200 days, as demonstrated functionally by C peptide secretion as well as by histology. These in vivo observations are consistent with the importance of donor HLA class I in eliciting graft rejection and have potential applicability to the successful transplantation of other HLA class I-bearing donor tissues.


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