T cell clonal expansions detected in patients with primary biliary cirrhosis express CX3CR1

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19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalJournal of Autoimmunity
Volume37
Issue number2
DOIs
StatePublished - Sep 2011

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Biliary Liver Cirrhosis
T-Lymphocytes
Autoantibodies
Chemokine CX3CL1
Technology
Phenotype
Virus Diseases
Autoimmune Diseases
Up-Regulation
Epithelial Cells

Keywords

  • Autoimmunity
  • CCR7
  • CX3CR1
  • Immunoscope
  • Primary biliary cirrhosis
  • T cell repertoire analysis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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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.",
keywords = "Autoimmunity, CCR7, CX3CR1, Immunoscope, Primary biliary cirrhosis, T cell repertoire analysis",
author = "Weici Zhang and Yoko Ono and Yoshinori Miyamura and Christopher Bowlus and Gershwin, {M. Eric} and Maverakis, {Emanual Michael}",
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AU - Maverakis, Emanual Michael

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AB - 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.

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