Peripheral blood T-cell responses to pyruvate dehydrogenase complex in primary biliary cirrhosis: role of antigen-presenting dendritic cells

Background Patients with primary biliary cirrhosis (PBC) are usually charac terized by the presence of antibody to pyruvate dehydrogenase complex (PDC) in the sera and PDC-specific T cells in the liver. However, most of the pa tients with PBC do not show peripheral blood T cells response to PDC. In th is study, we re-evaluated the peripheral blood T cell responses to PDC in P BC using antigen-presenting dendritic cells (DCs). Materials and Methods Twenty-four patients with PBC (AMA-positive: 16; AMA- negative: 8) and 13 normal controls were enrolled in the study. Peripheral blood mononuclear cells (PBMC) and highly enriched populations of T cells w ere stimulated with either only PDC or DCs plus PDC or PDC-pulsed DC plus P DC. Antibodies to different components of PDC were estimated by an immunobl otting technique. Results PBMC from only one out of ten AMA-positive PPC patients proliferate d when cultured with only PDC. However, peripheral blood T cells from ten o ut of ten AMA-positive PBC patients and three out of ten AMA-negative PBC p atients, but none of the five normal controls showed PDC-specific prolifera tion when cultured with PDC-pulsed DCs. Two of these three AMA-negative PBC patients, although negative for AMA, were positive for antibodies to other components of PDC. Conclusions PDC-specific T cells are present in the peripheral blood from m ost of the patients with PBC. This is the first report on the effectiveness of antigen-pulsed DCs for the elucidation of autoantigen-specific immune r esponse in human autoimmune diseases.