1988 Fiscal Year Final Research Report Summary
Autoimmunity to Bile Duct Epithelial Cells in Patients with Primary Billary Cirrhosis
| Project/Area Number |
62570329
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kochi Medical School |
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Principal Investigator |
ONISHI Saburo Kochi Medical School, 医学部, 講師 (60136380)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Takashi Kochi Medical School, 医学部, 助手 (80183606)
SAIBARA Toshiji Kochi Medical School, 医学部, 助手 (60145125)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Primary biliary cirrhosis / Cytotoxic T lymphocyte / Biliary duct epithelial antigen / B1抗原 |
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| Research Abstract |
Primary biliary cirrhosis (PBC) is an enigmatic chronic liver disease characterized by progressive and inflammatory obliteration of intrahepatic bile ducts where autoimmune-mediated pathogenesis is considered to be responsible for damages to the target tissue. We reported a predominant role of T cell mediated immunity in the pathogenesis of PBC, because peripheral lymphocytes were sensitized to partially purified biliary antigen in leukocyte migration inhibition test, while antibody to the same antigen was not detected in the sera of PBC patients.
In this study, histoimmunochemical investigation showed that OKT8 positive and Leul5 negative T cell population, phenotypically cytotoxic T cells infiltrated into damaged bile ducts in PBC. Furthermore, splenic T lymphocytes but not non-T lymphocytes were shown to be cytotoxic against autologous biliary epithelial( BE ) cells at effector to target ratios of 100 and 200 in 10hrs'^<51>Cr% release. BE cells were obtained from autopsy specimen by
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pumping PBS solution supplemented with EDTA, DNAase and Disparse into bile ducts. Specificity of cytotoxicity was shown by cold target inhibition using autologous BE cells. A phenotype of effectors was shown to be CD8 positive by negative selection using complement lysis with OKT8 or OKT4 monoclonal antibody. Next, biliary epithelial antigens were identified by SDS-PAGE and Western blotting of partially purified biliary antigen in which rabbit anti-biliary antigen specific to human biliary epithelial cells was used to detect the antigens. B1, B2 and B3 antigens with more than 200 KD mw were detected. They were eluted electophoretically from gels separately and used as antigens to stimulate T cell proliferation. Blastgensis to B1 at a constriction of 1.0 to 0.1 mc g/ml was detected exclusively in PBC but not in other liver diseases while blastgenesis to B3 was not detected in PBC.
These data strongly point to the role of T cell immunity against biliary epithelial antigen; B1 antigen in the pathogenesis of PBC. Less
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