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Prolongation of murine vascularized heart allograft survival by recipient-specific anti-major histocompatibility
R M Smith1, Z K Chen, R Foulkes
1Department of Academic Renal Medicine, Southmead Hospital, Westbury-on-Trym, Bristol, England.
Background:
Antibodies targeting recipient major histocompatibility complex (MHC) class II molecules have been demonstrated to be effective at prolonging allograft survival. However, antigen-presenting cell depletion would explain this effect and has not been definitively excluded as the mechanism of action of such antibodies. We have studied an anti-MHC class II antibody (OX6) proven to be noncytotoxic in the recipient strain used.
Methods:
Antibody was administered the day before, 2 hr before, and the day after grafting.
Results:
Antibody administration on the day before, 2 hr before, and the day after grafting significantly prolonged vascularized cardiac allograft survival. Importantly, treatment recognizing recipient MHC was effective, whereas a similar regimen recognizing donor MHC was not.
Conclusions:
Noncytotoxic recipient MHC class II-specific antibodies modify allograft rejection. Possible mechanisms for this therapeutic effect are discussed.