Immunological control in primary biliary cirrhosis: the cytokine story

Primary biliary cirrhosis (PBC) is characterized histologically by a progressive obliteration of intrahepatic bile ducts. In affected portal tracts the cellular infiltrate contains large numbers of T lymphocytes, and there is considerable evidence that they are important to the initiation and perpetuation of bile duct injury, although the cause of T helper (Th, CD4 ) cell activation remains unknown. The recent establishment of T cell clones has enabled T cell epitopes to be characterized. Reactivity to the dihydrolipoamide acetyltransferase moiety of pyruvate dehydrogenase (PDC-E2), the major target of the antmitochondrial antibody present in the sera of over 90% of patients, has been found in T cells isolated from blood [1] and liver [2,3], and such reactivity may be HLArestricted In other examples of organ-specific autoimmune diseases such as myasthenia gravis [5], autoimmune thyroiditis [6] and non-insulin-dependent diabetes