Novel model of antigen-specific induction of bile duct injury.

Novel model of antigen-specific induction of bile duct injury. Research Abstract Details 

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Novel model of antigen-specific induction of bile duct injury. Abstract Text:

James Buxbaum,Peiqing Qian,Ciera Khuu,Benjamin L Shneider,David I Daikh,M Eric Gershwin,Paul M Allen,Marion G Peters,

BACKGROUND & AIMS: Biliary-directed inflammation is an important cause of acute and chronic liver disease. We developed and characterized a transgenic mouse model of immune-mediated hepatobiliary injury. METHODS: Ovalbumin (OVA)-BIL mice were developed using 3.0 kilobase of the rat apical sodium-dependent bile acid transporter promoter to drive aberrant expression of a membrane form of ovalbumin (OVA) on biliary epithelium. Liver inflammation resulted from adoptive transfer of OVA-specific T cells. Liver immune cells were characterized to determine the mechanism of the response by assessing activation, proliferation, and intracellular cytokine expression. RESULTS: OVA-BIL transgenic mice were tolerant to OVA, without evidence of liver disease. Adoptive transfer of OVA-specific CD4+ and CD8+ T cells into naïve OVA-BIL mice led to biliary-centered necroinflammatory damage in a dose-dependent manner. This inflammation absolutely required CD8+ T cells and was augmented by CD4+ T cells. Adoptively transferred OVA CD8+ cells homed to and proliferated in the liver but not the spleen. These activated, adoptively transferred cytotoxic T lymphocytes produced elevated levels of tumor necrosis factor alpha and interferon gamma. CONCLUSIONS: T-cell recognition of antigen aberrantly expressed on bile duct epithelium induced an acute necroinflammatory response specific to the liver, with activation, proliferation, and cytokine production predominantly by the OVA-specific cytotoxic T cells. Thus, OVA BIL represents an antigen-specific animal model of inflammatory bile duct injury.

Novel model of antigen-specific induction of bile duct injury. Publishing Authors By Initials

J Buxbaum,P Qian,C Khuu,BL Shneider,DI Daikh,ME Gershwin,PM Allen,MG Peters,

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

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MEDLINE DATE:

Novel model of antigen-specific induction of bile duct injury. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Gastroenterology

VOLUME: 131

Page Numbers: 1899-906

Journal Abbreviation: Gastroenterology

ISSN: 0016-5085

DAY: 14

MONTH: 10

YEAR: 2006

Novel model of antigen-specific induction of bile duct injury. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 374630

Novel model of antigen-specific induction of bile duct injury. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: metabolism

Chemical & Substance for Abstract: Novel model of antigen-specific induction of bile duct injury. Information

Substance Name: Ovalbumin

Registry Number: 9006-59-1

Grant and Affiliation Information for Novel model of antigen-specific induction of bile duct injury.

AFFILIATION: Department of Medicine, University of California, San Francisco, California 94143-0538, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: P30 DK26743

ACRONYM: DK

MEDLINETA: Gastroenterology

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