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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 144-148 |
| Number of pages | 5 |
| Journal | Annals of Thoracic Surgery |
| Volume | 65 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Surgery
Cite this
Induction of tolerance in rodent cardiac allotransplantation using an MHC class I-derived peptide and cyclosporin A. / Masroor, Saqib; Itescu, Silviu; Artrip, John H.; Minanov, Oktavijan P.; Buelow, Roland; Michler, Robert E.
In: Annals of Thoracic Surgery, Vol. 65, No. 1, 01.1998, p. 144-148.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of tolerance in rodent cardiac allotransplantation using an MHC class I-derived peptide and cyclosporin A
AU - Masroor, Saqib
AU - Itescu, Silviu
AU - Artrip, John H.
AU - Minanov, Oktavijan P.
AU - Buelow, Roland
AU - Michler, Robert E.
PY - 1998/1
Y1 - 1998/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031907870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031907870&partnerID=8YFLogxK
U2 - 10.1016/S0003-4975(97)01258-7
DO - 10.1016/S0003-4975(97)01258-7
M3 - Article
C2 - 9456108
AN - SCOPUS:0031907870
VL - 65
SP - 144
EP - 148
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
SN - 0003-4975
IS - 1
ER -