T-CELL RESPONSES TO THE COMPONENTS OF PYRUVATE-DEHYDROGENASE COMPLEX IN PRIMARY BILIARY-CIRRHOSIS

Primary biliary cirrhosis (PBC) is an autoimmune condition that result s in destruction of the intrahepatic biliary epithelial cells and is c haracterized by autoantibodies to pyruvate dehydrogenase complex (PDC) . The portal tract T-cell infiltrate and up-regulation of HLA class I, HLA class II, and cell adhesion molecules such as intercellular adhes ion molecule-1 on the biliary epithelial cells suggest that T cells pl ay a significant rol in mediating this damage. The authors have charac terized the peripheral blood T-cell proliferative responses of 24 PBC patients and 48 controls (20 normal, 28 non-PBC chronic liver disease) to the dominant autoantigen PDC, and its constituent components E1, E 2 and protein X (which co-purify), and E3. A significant proportion of both PBC patients and controls showed T-cell responses to whole PDC ( 12 of 24 vs, 24 of 48 SI > 2.5 P = NS) and E1 (15 of 24 vs. 25 of 48 P = NS). Responses to PDC and E1 are thus seen in normal individuals an d are not limited to PBC patients. T-cell responses to E2/X were seen in most PBC patients (14 of 24), but in only a small number of control s (6 of 48, P < .0001), responses to E2/X being significantly more fre quent in pre-cirrhotic PEC patients (stages I to III, 12 of 15) than c irrhotic (stage IV, 2 of 9 P < .06). Peripheral blood T-cell responses to E2/X are thus strongly associated with early PBC. Responses to E3 were low in both PBC patients and controls. No differences were seen i n responses to the control antigen tetanus toroid between PBC patients and controls. These in vitro observations are compatible with the vie w that peripheral mechanisms may play a significant role in maintainin g self-tolerance to PDC in the normal state, and that the expression o f specific T-cell responses to PDC-E2/X in vivo in PEC patients may be a consequence of impairment of these mechanisms of peripheral toleran ce.