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Relationship of CD146 expression to activation of circulating T cells: exploratory studies in healthy donors and patients with connective tissue diseases.

Abstract
The endothelial cell adhesion molecule, CD146, is expressed on ≈ 2% of normal circulating T cells, correlating with T cell activation, endothelial interactions and T helper type 17 (Th17) effector functions. In this study, we have characterized CD146 expression in circulating T cells from healthy controls and patients with stable, well-controlled autoimmune connective tissue diseases (CTDs). In vitro, anti-CD3/anti-CD28 stimulation induced CD146 expression in both CD4 and CD8 T cells. In healthy controls and CTD patients, CD146 was associated with expression of recent and chronic activation markers (CD25(+), OX-40(+), CD69(+), CD27(-)) and was confined to CD45RO(+)/RA(-)/CD28(+) populations within the CD4 subset. Except for CD69, these markers were not associated with CD146 in the CD8 subset. Surprisingly, most CTD patients exhibited no T cell hyperactivation ex vivo. In five of five patients with secondary Sjögren's syndrome circulating T cells appeared activated despite therapy, and CD146 up-regulation, associated with activation markers, was observed both on CD4 and CD8 T cells. There was no association between CD146 and putative pro-atherogenic T cell subsets. In conclusion, the relationship of CD146 expression to T cell activation differs between T cell subsets in healthy subjects and correlates with systemic hyperactivity, where present, in patients with CTDs, as exemplified by the patients with secondary Sjögren's syndrome in this study.
AuthorsA V Hadjinicolaou, L Wu, B Fang, P A Watson, F C Hall, R Busch
JournalClinical and experimental immunology (Clin Exp Immunol) Vol. 174 Issue 1 Pg. 73-88 (Oct 2013) ISSN: 1365-2249 [Electronic] England
PMID23738744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 British Society for Immunology.
Chemical References
  • CD146 Antigen
  • MCAM protein, human
Topics
  • Adult
  • Aged
  • Atherosclerosis (immunology, pathology)
  • CD146 Antigen (biosynthesis, blood)
  • Connective Tissue Diseases (immunology, metabolism, pathology)
  • Female
  • Humans
  • Immunophenotyping
  • Lupus Erythematosus, Systemic (immunology, pathology)
  • Lymphocyte Activation (immunology)
  • Male
  • Middle Aged
  • Scleroderma, Systemic (immunology, metabolism, pathology)
  • Sjogren's Syndrome (immunology, metabolism, pathology)
  • T-Lymphocyte Subsets (immunology, metabolism, pathology)
  • Young Adult

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