Different in vivo tolerogenicity of MHC class I peptides

The efficacy of MHC class I‐derived peptides to induce tolerance was tested in a cardiac transplantation model. Two 25‐mer peptides from the polymorphic region of the DA class I molecule (RT1.Aa) were synthesized by F‐moc chemistry and injected intrathymically or intraperitoneally into LEW (RT1.1) r...

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Bibliographic Details
Published in:	Journal of leukocyte biology Vol. 65; no. 1; pp. 16 - 27
Main Authors:	Fandrich, Fred, Zhu, Xiaofung, Schröder, Jörg, Dresske, Bettina, Henne‐Bruns, Doris, Oswald, Hanno, Zavazava, Nicholaus
Format:	Journal Article
Language:	English
Published:	United States Society for Leukocyte Biology 01-01-1999
Subjects:	Animals cardiac transplantation model Cytokines - biosynthesis Cytotoxicity, Immunologic Gene Expression Graft Rejection - immunology Graft Rejection - pathology Graft Survival - immunology Heart Transplantation - immunology Histocompatibility Antigens Class I - immunology Immune Tolerance Interleukin-10 - biosynthesis Interleukin-4 - biosynthesis interleukin‐10 interleukin‐4 Isoantigens - immunology Killer Cells, Natural - immunology Lymphocyte Activation Lymphocytes - immunology Male Myocardium - metabolism Myocardium - pathology Peptide Fragments - chemical synthesis Peptide Fragments - immunology Peptide Fragments - pharmacology Rats Rats, Inbred Lew Skin Transplantation - immunology T-Lymphocytes - cytology T-Lymphocytes - immunology transforming growth factor β Up-Regulation
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Summary:	The efficacy of MHC class I‐derived peptides to induce tolerance was tested in a cardiac transplantation model. Two 25‐mer peptides from the polymorphic region of the DA class I molecule (RT1.Aa) were synthesized by F‐moc chemistry and injected intrathymically or intraperitoneally into LEW (RT1.1) responder animals. Intrathymic treatment of the recipient animals with peptide 1 (residues 56–80) accompanied by intraperitoneal treatment with peptide 4 (residues 96–120) led to indefinite survival of allogeneic DA cardiac allografts (n = 7; >100 days). The tolerogenicity of both peptides differed according to the site of inoculation, as donor‐specific tolerance was only observed after administration of peptide 1 into the thymus and injection of peptide 2 into the abdominal cavity of LEW recipients, but not vice versa. Donor‐specific tolerance was confirmed in vivo by grafting of full‐thickness skin and in vitro by appropriate proliferation and cytotoxicity assays using donor and third‐party rats. Donor‐specific tolerance was associated with up‐regulation of interleukin‐4, transforming growth factor β, and interleukin‐10 gene expression within cardiac allografts, thus suggesting intrathymic clonal deletion and external suppression with expansion of T‐helper 2‐type lymphocytes as the underlying mechanisms of tolerance induction. J. Leukoc. Biol. 65: 16‐27; 1999.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0741-5400 1938-3673
DOI:	10.1002/jlb.65.1.16