| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
|
|---|
| Research Abstract |
To determine the autoantigen involved in the bile duct injury in primary biliary cirrhosis (PBC), we purified antigens from human bile juice using SDS-PAGE and Western blotting (WB). In WB, rabbit anti human biliary epithelium was used as a monitoring probe. Corresponding antigen of rabbit antisera was proved to exist on microvilli, but not on the bile canaliculi by immuno-electron microscopic examination. Two major protein bands (B1, B2) were detected in WB. Proliferation of peripheral lymphocytes against B1 was observed selectively in patients of PBC, but not in control diseases. B1 stimulated T cells and was free of direct B cell mitogen. This T cell proliferation was inhibited by anti MHC class I monoclonal antibody. However, B2 was not stimulatory in PBC.
B1 was sialic protein and negative for lipid staining. M. W. of B1 was more than 200K. D.. In WB, B1 was not detected by antisecretory IgA, anti laminin, type IV collagen, anti M2 positive PBC sera, or anti MHC class antigen.
Secondary, cytotoxicity of spleen lymphocytes from PBC patients was against autologous biliary epithelial cells which were obtained by pumping Disparse solution through common bile ducts. Phenotype of Effector cells was CD8 positive T lymphocytes. CTL activity was inhibited by anti MHC class I, but not by anti MH class II.
In conclusion, T cell autoimmunity against B1 may be involved in the pathogenesis of PBC.
|
