Journal
JOURNAL OF AUTOIMMUNITY
Volume 37, Issue 2, Pages 71-78Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2011.05.009
Keywords
Autoimmunity; Immunoscope; Primary biliary cirrhosis; CX3CR1; T cell repertoire analysis; CCR7
Categories
Funding
- NIDDK NIH HHS [R01 DK039588] Funding Source: Medline
- NIH HHS [DP2 OD008752] Funding Source: Medline
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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 TCRV beta 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. Published by Elsevier Ltd.
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