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dc.contributor.authorRadstake, Timothy R. D. J.en_US
dc.contributor.authorvan Bon, Lennyen_US
dc.contributor.authorBroen, Jasperen_US
dc.contributor.authorWenink, Marken_US
dc.contributor.authorSantegoets, Kimen_US
dc.contributor.authorDeng, Yanhuien_US
dc.contributor.authorHussaini, Anilaen_US
dc.contributor.authorSimms, Roberten_US
dc.contributor.authorCruikshank, William W.en_US
dc.contributor.authorLafyatis, Roberten_US
dc.date.accessioned2012-01-11T22:31:12Z
dc.date.available2012-01-11T22:31:12Z
dc.date.issued2009-6-22en_US
dc.identifier.citationRadstake, Timothy R. D. J., Lenny van Bon, Jasper Broen, Mark Wenink, Kim Santegoets, Yanhui Deng, Anila Hussaini, Robert Simms, William W. Cruikshank, Robert Lafyatis. "Increased Frequency and Compromised Function of T Regulatory Cells in Systemic Sclerosis (SSc) Is Related to a Diminished CD69 and TGF Expression" PLoS ONE 4(6): e5981. (2009)en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/2144/3309
dc.description.abstractBACKGROUND. Regulatory T cells (Tregs) are essential in the control of tolerance. Evidence implicates Tregs in human autoimmune conditions. Here we investigated their role in systemic sclerosis (SSc). METHODS/PRINCIPAL FINDINGS. Patients were subdivided as having limited cutaneous SSc (lcSSc, n=20) or diffuse cutaneous SSc (dcSSc, n=48). Further subdivision was made between early dcSSc (n=24) and late dcSSc (n=24) based upon the duration of disease. 26 controls were studied for comparison. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, FoxP3, CD127, CD62L, GITR, CD69 using flow cytometry. T cell suppression assays were performed using sorted CD4CD25highCD127- and CD4CD25lowCD127high and CD3+ cells. Suppressive function was correlated with CD69 surface expression and TGFβ secretion/expression. The frequency of CD4+CD25+ and CD25highFoxP3highCD127neg T cells was highly increased in all SSc subgroups. Although the expression of CD25 and GITR was comparable between groups, expression of CD62L and CD69 was dramatically lower in SSc patients, which correlated with a diminished suppressive function. Co-incubation of Tregs from healthy donors with plasma from SSc patients fully abrogated suppressive activity. Activation of Tregs from healthy donors or SSc patients with PHA significantly up regulated CD69 expression that could be inhibited by SSc plasma. CONCLUSIONS/SIGNIFICANCE. These results indicate that soluble factors in SSc plasma inhibit Treg function specifically that is associated with altered Treg CD69 and TGFβ expression. These data suggest that a defective Treg function may underlie the immune dysfunction in systemic sclerosis.en_US
dc.description.sponsorshipNiels-Stensen Foundation from The Netherlands Dutch Organization of Research; National Institutes of Health (NIAMS U01AR055063); American Society for Scleroderma Research.en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.titleIncreased Frequency and Compromised Function of T Regulatory Cells in Systemic Sclerosis (SSc) Is Related to a Diminished CD69 and TGFβ Expressionen_US
dc.typearticleen_US
dc.identifier.doi10.1371/journal.pone.0005981en_US
dc.identifier.pubmedid19543397en_US
dc.identifier.pmcid2695559en_US


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