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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

References

  1. Induction of tolerance in rodent cardiac allotransplantation using an MHC class I-derived peptide and cyclosporin A. Masroor, S., Itescu, S., Artrip, J.H., Minanov, O.P., Buelow, R., Michler, R.E. Ann. Thorac. Surg. (1998) [Pubmed]
 
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