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Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
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Immortalized intrahepatic mouse biliary epithelial cells: immunologic characterization and immunogenicity
G Hreha1, D M Jefferson, C H Yu
1Center for Liver Diseases and Transplantation, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hepatology (Baltimore, Md.)
|July 27, 1999
Summary
Researchers developed immortalized mouse biliary cells to study nonsuppurative destructive cholangitis (NSDC) in a graft-versus-host disease (GVHD) model. These cells retain their phenotype and form immunogenic structures, aiding immunopathogenesis research.
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Background:
- Nonsuppurative destructive cholangitis (NSDC) involves T-cell-mediated destruction of biliary epithelia.
- NSDC is observed in primary biliary cirrhosis, graft-versus-host disease (GVHD), and hepatic allograft rejection (HAR).
- A B10.D2-->BALB/c murine model exhibits GVHD-associated NSDC, necessitating reliable target cells for immunopathogenesis studies.
Purpose of the Study:
- To immortalize BALB/c intrahepatic biliary epithelial cells (BEC) for use as target cells in the B10.D2-->BALB/c GVHD model.
- To characterize the phenotype and immunogenic potential of immortalized BEC.
- To facilitate future research into the immunopathogenesis of NSDC.
Main Methods:
- Immortalization of 4 BALB/c intrahepatic BEC lines using SV40 large T antigen.
- Phenotypic characterization including expression of cytokeratin-19 (CK-19), EPCAM, CFTR, MHC class I and II, ICAM-1, B7-1/B7-2, and FAS.
- Assessment of BEC immunogenicity via injection into BALB/c and B10.D2 mice and observation of inflammatory responses.
Main Results:
- Immortalized BEC retained the phenotype of freshly isolated BEC, expressing CK-19, EPCAM, and CFTR.
- Interferon gamma (IFN-gamma) induced aberrant class II MHC and increased ICAM-1 expression.
- In vivo injection of immortalized BEC resulted in duct-like structures that elicited inflammatory lesions reminiscent of NSDC in B10.D2 recipients.
Conclusions:
- BALB/c-immortalized intrahepatic BEC lines serve as valuable tools for studying NSDC immunopathogenesis.
- These cell lines retain key BEC characteristics and exhibit immunogenic properties.
- The developed cell lines are suitable for advancing research in the B10.D2-->BALB/c GVHD model of NSDC.
