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Peripheral blood T‐cell responses to pyruvate dehydrogenase complex in primary biliary cirrhosis: role of antigen‐presenting dendritic cells
Author(s) -
Akbar S. M. F.,
Yamamoto K.,
Miyakawa H.,
Ninomiya T.,
Abe M.,
Hiasa Y.,
Masumoto T.,
Horiike N.,
Onji M.
Publication year - 2001
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2001.00847.x
Subject(s) - primary biliary cirrhosis , peripheral blood mononuclear cell , antigen , immunology , antibody , immune system , dendritic cell , medicine , t cell , antigen presenting cell , biology , in vitro , biochemistry
Patients with primary biliary cirrhosis (PBC) are usually characterized 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 patients with PBC do not show peripheral blood T cells response to PDC. In this study, we re‐evaluated the peripheral blood T cell responses to PDC in PBC using antigen‐presenting dendritic cells (DCs). 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 were stimulated with either only PDC or DCs plus PDC or PDC‐pulsed DC plus PDC. Antibodies to different components of PDC were estimated by an immunoblotting technique. PBMC from only one out of ten AMA‐positive PBC patients proliferated when cultured with only PDC. However, peripheral blood T cells from ten out of ten AMA‐positive PBC patients and three out of ten AMA‐negative PBC patients, but none of the five normal controls showed PDC‐specific proliferation 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. PDC‐specific T cells are present in the peripheral blood from most of the patients with PBC. This is the first report on the effectiveness of antigen‐pulsed DCs for the elucidation of autoantigen‐specific immune response in human autoimmune diseases.