Cellular mechanism of immunopathogenesis of primary biliary cirrhosis

Primary biliary cirrhosis(PBC) is a progressive,organ-specific autoimmune disease that predominantly affects woman and is characterized by lymphocytic infiltration in portal tracts,immune-mediated destruction of small intrahepatic small bile ducts,and the presence of high titers of serum anti-mitochondrial Abs(AMAs).A murine model of PBC,generated by expressing a dominant-negative form of TGFβ receptor type Ⅱ(dnTGFβRⅡ) under the direction of the CD4 promoter,demonstrates several key features of human PBC and has been applied in previous PBC studies.Experimental data from Rag1-/-,μ-/-and CD1d-/-mice on a dnTGFβRⅡ background indicated that T cells,B cells and CD1d-restricted NKT cells plays critical roles in liver injury.Moreover,based on a rigorous series of cellular immunological studies,it is concluded that CD8+,but not CD4+ T cells,play a prominent role in mediating pathogenesis,and that B cells can have a suppressive regulatory effect on the infiammatory response besides just secreting auto-antibodies.These studies provide substantial evidence for a cellular mechanism in human primary biliary cirrhosis pathogenesis.