Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease

Approximately 25% of subjects with common variable immunodeficiency (CVID) develop autoimmune disease. We analyzed T cell subsets, specifically regulatory T cells along with B cell subsets to determine whether there were changes in regulatory T cells which would correlate with the autoimmune disease...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 131(2009), 2 vom: 02. Mai, Seite 240-53
1. Verfasser: Yu, Grace P (VerfasserIn)
Weitere Verfasser: Chiang, David, Song, Steven J, Hoyte, Elisabeth G, Huang, Jennifer, Vanishsarn, Christopher, Nadeau, Kari C
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2009
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Leukocyte Common Antigens EC 3.1.3.48
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520 |a Approximately 25% of subjects with common variable immunodeficiency (CVID) develop autoimmune disease. We analyzed T cell subsets, specifically regulatory T cells along with B cell subsets to determine whether there were changes in regulatory T cells which would correlate with the autoimmune disease clinical phenotype in CVID subjects. We hypothesized that regulatory T cell (CD4+CD25hiCD127lo) suppressive function would be impaired in CVID subjects with autoimmune disease. Using purified, sorted Treg from CVID subjects (n=14) and from healthy controls (HC, n=5) in standard suppression assays, we found the suppressive function of Treg from CVID subjects with autoimmune disease (CVID w/ AI, n=8) to be significantly attenuated compared to CVID subjects with no autoimmune disease (CVID w/o AI, n=6) and to HC (n=5). A number of proteins associated with Treg function were decreased in expression as detected through immunofluorescent antibody via flow cytometry (mean fluorescence intensity (MFI) of FoxP3, Granzyme A, XCL1, pSTAT5, and GITR in Treg was significantly lower (by up to 3 fold) in CVID w/ AI compared to CVID w/o AI and HC. Furthermore, a statistically significant correlation was found between intracellular MFI of FoxP3, Granzyme A, and pSTAT5 in Treg and the degree of Treg dysfunction. These results suggest that attenuation of Treg function is associated with autoimmune disease in CVID subjects and may contribute to autoimmune pathogenesis 
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700 1 |a Chiang, David  |e verfasserin  |4 aut 
700 1 |a Song, Steven J  |e verfasserin  |4 aut 
700 1 |a Hoyte, Elisabeth G  |e verfasserin  |4 aut 
700 1 |a Huang, Jennifer  |e verfasserin  |4 aut 
700 1 |a Vanishsarn, Christopher  |e verfasserin  |4 aut 
700 1 |a Nadeau, Kari C  |e verfasserin  |4 aut 
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