Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins.

Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins. Research Abstract Details 

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Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins. Abstract Text:

John Perez,Stanislaw M Stepkowski,Ping Song,Barton Trawick,Mou-Er Wang,Slawa Janczewska,Barry D Kahan,John Perez,Stanislaw M Stepkowski,Ping Song,Barton Trawick,Mou-Er Wang,Slawa Janczewska,Barry D Kahan,

BACKGROUND: Ten different highly polymorphic amino acids (AAs) are located in the alpha1 (alpha1h) and alpha2 (alpha2h) helical regions of the class I major histocompatibility complex RT1.An rat alloantigen. We examined the potential of alpha1h-RT1.An versus alpha2h-RT1.An polymorphic AAs to induce accelerated rejection or tolerance of heart allografts. METHODS: The allochimeric alpha1h52-90n-RT1.Ac and alpha2h148-179n-RT1.Ac cDNAs were produced by the substitution of nucleotides encoding recipient RT1.Ac AAs for donor RT1.An AAs. Allochimeric and wild-type (WT)-RT1.An proteins were generated in an Escherichia coli expression system. RESULTS: A single portal vein administration of 100 mug alpha1h52-90n-RT1.Ac protein in combination with a 7-day course of oral cyclosporine A (4 mg/kg) induced tolerance to Brown Norway (BN) (RT1n) heart allografts in PVG (RT1c) recipients more effectively than did WT-RT1.An protein; alpha2h148-179n-RT1.Ac protein was ineffective. However, subcutaneous injection of 100 mug WT-RT1.An (but neither alpha1h52-90n-RT1.Ac nor alpha2h148-179n-RT1.Ac) protein induced accelerated rejection of BN heart allografts. Untreated PVG recipients of BN heart allografts displayed activation of both interleukin (IL)-2- and interferon-gamma-producing T helper (Th) 1 cells and IL-4- and IL-10-producing Th2 cells on days 5, 7, and 14 postgrafting, as measured by an enzyme-linked immunospot assay. In contrast, in comparison with rejectors, tolerant recipients showed down-regulation of Th1 cells and up-regulation of Th2 cells on days 5, 7, 14, and 200 postgrafting. Histology of heart allografts showed that tolerant BN heart allografts had no evidence of acute or chronic rejection when examined on day 100 after transplantation. CONCLUSIONS: The poorly immunogenic alpha1h52-90n-RT1.Ac allochimeric protein induces tolerance by selective activation of regulatory Th2 cells.

Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins. Publishing Authors By Initials

J Perez,SM Stepkowski,P Song,B Trawick,ME Wang,S Janczewska,BD Kahan,J Perez,SM Stepkowski,P Song,B Trawick,ME Wang,S Janczewska,BD Kahan,

For similar surgical procedures, operative: transplantation: transplantation, homologous research abstracts see: surgical procedures, operative: transplantation: transplantation, homologous research

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Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Transplantation

VOLUME: 76

Page Numbers: 1201-7

Journal Abbreviation: Transplantation

ISSN: 0041-1337

DAY: 27

MONTH: Oct

YEAR: 2003

Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins. Information

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LANGUAGE: eng

NlmUniqueID: 132144

Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins. Keywords Mesh Terms:

KEYWORDS: Transplantation, Homologous

MESH TERMS: immunology

Chemical & Substance for Abstract: Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins. Information

Substance Name: histocompatibility antigens RT, rat

Registry Number: 0

Grant and Affiliation Information for Selection of lowly immunogenic and highly tolerogenic donor and recipient allochimeric class I major histocompatibility complex proteins.

AFFILIATION: Department of Surgery, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL 69723

ACRONYM: HL

MEDLINETA: Transplantation

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