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Ann Thorac Surg. 1998 Jan;65(1):144-8.

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

Author information

1
Division of Cardiothoracic Surgery, Columbia-Presbyterian Medical Center, New York, New York, USA.

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.

PMID:
9456108
DOI:
10.1016/s0003-4975(97)01258-7
[Indexed for MEDLINE]

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