       Document 0107
 DOCN  M9620107
 TI    [Infiltrating T-cells in primary biliary cirrhosis recognize
       mitochondrial epitopes]
 DT    9602
 AU    Lohr H; Fleischer B; Gerken G; Meyer zum Buschenfelde KH; Manns M; I.
       Medizinische Klinik und Poliklinik, Universitat Mainz.
 SO    Z Gastroenterol. 1993 Feb;31 Suppl 2:99-103. Unique Identifier :
       AIDSLINE MED/96029866
 AB    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)
 DE    Antigen-Presenting Cells/IMMUNOLOGY  Autoantibodies/BLOOD
       Autoantigens/*IMMUNOLOGY  B-Lymphocytes/IMMUNOLOGY  CD4-CD8 Ratio
       CD4-Positive T-Lymphocytes/IMMUNOLOGY  English Abstract
       Epitopes/IMMUNOLOGY  Hepatitis B/IMMUNOLOGY  Hepatitis, Chronic
       Active/IMMUNOLOGY  Histocompatibility Antigens Class II/IMMUNOLOGY
       Human  Liver Cirrhosis, Biliary/*IMMUNOLOGY  Liver Function Tests
       Mitochondria, Liver/*IMMUNOLOGY  Subcellular Fractions/IMMUNOLOGY
       T-Lymphocytes/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

