Increased Frequency and Compromised Function of T Regulatory Cells in Systemic Sclerosis (SSc) Is Related to a Diminished CD69 and TGFβ Expression

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dc.contributor.author Radstake, Timothy R. D. J. en_US
dc.contributor.author van Bon, Lenny en_US
dc.contributor.author Broen, Jasper en_US
dc.contributor.author Wenink, Mark en_US
dc.contributor.author Santegoets, Kim en_US
dc.contributor.author Deng, Yanhui en_US
dc.contributor.author Hussaini, Anila en_US
dc.contributor.author Simms, Robert en_US
dc.contributor.author Cruikshank, William W. en_US
dc.contributor.author Lafyatis, Robert en_US
dc.date.accessioned 2012-01-11T22:31:12Z
dc.date.available 2012-01-11T22:31:12Z
dc.date.issued 2009-6-22 en_US
dc.identifier.citation Radstake, 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.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/3309
dc.description.abstract BACKGROUND. 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.sponsorship Niels-Stensen Foundation from The Netherlands Dutch Organization of Research; National Institutes of Health (NIAMS U01AR055063); American Society for Scleroderma Research. en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title Increased Frequency and Compromised Function of T Regulatory Cells in Systemic Sclerosis (SSc) Is Related to a Diminished CD69 and TGFβ Expression en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0005981 en_US
dc.identifier.pubmedid 19543397 en_US
dc.identifier.pmcid 2695559 en_US

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