期刊
CLINICAL IMMUNOLOGY
卷 131, 期 2, 页码 240-253出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2008.12.006
关键词
Common variable immunodeficiency; T-lymphocytes; Regulatory; Autoimmunity; Immunologic deficiency syndromes; Granzymes; Lymphotactin; Xcl1 protein, human; FOXP3 protein, human; TNFRSF18 protein, human; STAT5 transcription factor
类别
资金
- Stanford Children's Health Research Program and the Immunity, Transplantation and Infectious Disease Institute at Stanford University School of Medicine.
Approximately 25% of subjects with common variable immunodeficiency (CVID) develop autoimmune disease. We analyzed Tcell subsets, specifically regulatory Tcells 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 Tcell (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/ Al, n=8) to be significantly attenuated compared to CVID subjects with no autoimmune disease (CVID w/o Al, 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/Al compared to CVID w/o Al 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. (C) 2009 Elsevier Inc. All rights reserved.
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