[Infiltrating T-cells in primary biliary cirrhosis recognize mitochondrial epitopes]

The primary biliary cirrhosis (PBC) is characterized by lymphoid infiltrates in the portal tracts of the liver and occurrence of antimitochondrial autoantibodies (AMA) in serum directed against the pyruvate dehydrogenase complex or other enzyme complexes that are located on the inner mitochondrial membranes. The destruction of the biliary tracts is thought to be mediated by autoreactive liver infiltrating T-cells. In this study we demonstrate the reactivity of peripheral and liver-infiltrating T-cells against a crude preparation of human liver subcellular fractions measured by the tritium-thymidine uptake. Peripheral blood mononuclear cells (PBMC) from 13 of 15 patients with PBC and from 3 of 9 patients with chronic autoimmune hepatitis recognized human liver mitoplasts, i.e. mitochondria depleted of their outer membranes. PBMC from patients with chronic viral hepatitis B and C or with extrahepatic cholestatic icterus and PBMC from healthy controls did not recognize this antigen. Monoclonal antibodies against HLA-class II molecules blocked this proliferative response. Clonal analysis of 115 liver-infiltrating T-cells derived from two diagnostic liver biopsies of patients with PBC revealed a predominance of activated CD4+CD8- T helper cells. Six CD4- positive T-cell clones were reactive to the HLM preparation when the antigen was presented by autologous B cell lines. MAb against HLA-class II or HLA-DR inhibited the response whereas mAb against HLA-DP did not. These clones did not respond to other subcellular fractions of human liver tissue. We conclude that among liver-infiltrating T-cells in PBC autoreactive T-cells exist that recognize some epitopes on the inner mitochondrial membranes.(ABSTRACT TRUNCATED AT 250 WORDS)