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DOI: 10.1177/1522162802005003003 © 2002 SAGE Publications Immunomodulation with MHC Class II Peptides after Small Bowel Transplantation: Influence on Rejection and Outcome
T-cell recognition of allogeneic major histocompatibility complex (MHC) peptides presented by self-MHC molecules initiates allograft rejection. Under certain conditions, synthetic MHC peptides are able to inhibit the allogeneic T-cell response. The present study was designed to evaluate the effect of MHC class II peptides RT1.D2 and RT1.B2, corresponding to the hypervariable domain of Wistar Furth (WF) rat, combined with low-dose cyclosporine A (CsA) in experimental small bowel transplantation. In the rat strain combination WF-to-LEW, preoperatively administered RT1.B2 peptide (50 µg per rat) (but not RT1.D2 peptide) showed immunoinhibitory effects were seen and allograft survival was prolonged to a mean of 106 ±24.3 days in 43% of the Lewis graft (LEW) recipients. The graft survival after CsA application alone was limited to 49.9 ±8.3 days. In combination with peptide RT1.D2, the survival time was 47.1 ±3.8 days. The authors have evidence that the combination of CsA with peptide RT1.B2 induces specific unresponsive-ness in alloreactive T-cells. These promising results indicate that it is possible to suppress the T-cell-dependent alloresponse by the indirectly presented MHC class II peptide RT1.B2 in combination with low-dose CsA, to prolong small bowel allograft survival.
Key Words: allorecognition • MHC • peptides • T cells • Cyclosporin A
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