Peripheral blood T-cell responses to pyruvate dehydrogenase complex in primary biliary cirrhosis: role of antigen-presenting dendritic cells.
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.
Akbar
S M
SM
Ehime University School of Medicine, Ehime, Japan, Teikyo University Mizonokuchi Hospital, Kanagawa, Japan. onjimori@m.ehime-u.ac.jp
Yamamoto
K
K
Miyakawa
H
H
Ninomiya
T
T
Abe
M
M
Hiasa
Y
Y
Masumoto
T
T
Horiike
N
N
Onji
M
M
D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D001323:Autoantibodies; D011768:Pyruvate Dehydrogenase Complex