title: T cell clonal expansions detected in patients with primary biliary cirrhosis express CX3CR1.
abstract: The intrahepatic biliary destruction of primary biliary cirrhosis (PBC) appears secondary to a multi-lineage response that includes autoantibodies, biliary apotopes, and cellular responses. Although there has been considerable effort in defining the role and specificity of anti-mitochondrial autoantibodies, a major challenge has been the characterization of T effector pathways. This difficulty is due in part to the limitation of current technologies for directly isolating and characterizing autoreactive T cells from patients. Herein, we successfully demonstrate a novel technology for characterizing the surface phenotype of T cell oligoclonal expansions directly ex vivo. Using PBC as a prototypic disease we were able to detect clonal T cell expansions in 15/15 patients examined. Although the T cell expansions from different patients expressed different TCRVβ gene segments, the surface phenotype of the cells was the same. The clonal T cell expansions in PBC patients are CX3CR1(+) Fas(+) effector-memory T cells, a finding of particular importance given the known up-regulation of fractalkine on injured biliary epithelial cells (BEC). In contrast to the persistent aberrantly expanded T cells observed in the PBC patients, T cell expansions detected in response to a herpes viral infection were very dynamic and resolved over time. This protocol can be used to characterize T cell expansions in other autoimmune diseases.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, Davis, CA, USA.
authors.forename: Weici
authors.initials: W
authors.lastname: Zhang
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ono
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyamura
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Bowlus
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Emanual
authors.initials: E
authors.lastname: Maverakis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015551:Autoimmunity; D001652:Bile Ducts / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D048708:Cell Growth Processes; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D002999:Clone Cells; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine; D019014:fas Receptor