title: 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.
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Hadjinicolaou
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: B
authors.initials: B
authors.lastname: Fang
authors.forename: P A
authors.initials: PA
authors.lastname: Watson
authors.forename: F C
authors.initials: FC
authors.lastname: Hall
authors.forename: R
authors.initials: R
authors.lastname: Busch
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology; D051929:CD146 Antigen / Q000096:biosynthesis / Q000097:blood; D003240:Connective Tissue Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human
keywords: CD146/MelCAM; T lymphocyte subsets; autoimmune connective tissue diseases; flow cytometry; vascular/immune interactions