Induction of tolerance in rodent cardiac allotransplantation using an MHC class I-derived peptide and cyclosporin A

  • Ann Thorac Surg. 1998 Jan;65(1):144-8. doi: 10.1016/s0003-4975(97)01258-7.
S Masroor  1 ,  S Itescu ,  J H Artrip ,  O P Minanov ,  R Buelow ,  R E Michler
Affiliations
  • 1. Division of Cardiothoracic Surgery, Columbia-Presbyterian Medical Center, New York, New York, USA.
PMID: 9456108 DOI: 10.1016/s0003-4975(97)01258-7
Abstract

Background: The synthetic peptide corresponding to residues 75-84 of the human major histocompatibility complex class I molecule HLA-B7 (Allotrap 07) has been shown to inhibit differentiation of cytotoxic T lymphocyte precursors. Subsequent treatment of LEW-1A rats with this peptide was associated with a reduction in the level of cytotoxic activity directed to donor alloantigens. This study was undertaken to investigate the effect of Allotrap 07 on rodent heart allograft survival in LEW-1A recipients.

Methods: Heart allografts from Lewis rats were heterotopically transplanted into the infrarenal abdominal aorta of ACI recipients. The treatment groups consisted of different regimens of short-term intravenous Allotrap 07 and oral cyclosporin A. All grafts were palpated daily, with rejection defined as the cessation of palpable contractions.

Results: Cardiac allografts transplanted from Lewis to ACI rats survived indefinitely after administration of intravenous Allotrap 07 and oral cyclosporin A. Tolerance induction was donor-specific because third-party Brown-Norway, but not Lewis, grafts were rapidly rejected after implantation into ACI recipients.

Conclusions: Because donor-specific tolerance persisted long after cessation of peptide administration and did not occur when cyclosporin A was omitted from the immunosuppressive regimen, the mechanism may involve induction of clonal anergy.

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