Endocrinol Metab > Volume 22(5); 2007 > Article
Journal of Korean Endocrine Society 2007;22(5):332-338.
DOI: https://doi.org/10.3803/jkes.2007.22.5.332    Published online October 1, 2007.
Suppression of Pathogenic Autoreactive CD4+ T Cells by CD137-mediated Expansion of CD4+CD25+ Regulatory T Cells in Graves' Disease.
Eun Sook Kim, Hyo Won Jung, Jung Il Choi, Il Seung Nam-Goong, Soon Hyung Hong, Young Il Kim
1Department of Internal Medicine, Ulsan University Hospital, Ulsan University of Collage of Medicine.
2Biomedical Research Center, Ulsan University Hospital, Ulsan University of Collage of Medicine.
Abstract
BACKGROUND
Graves' disease (GD) is an organ-specific autoimmune disease that is characterized by lymphocyte infiltration of the thyroid, which finally leads to follicular destruction. The CD4+CD25+ regulatory T cells are important for maintaining peripheral tolerance to self-antigens and impaired activity can cause autoimmune diseases. CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily and expressed on activated T cells, is a candidate molecule for a co-stimulatory role in autoimmune thyroid disease. In this study, we aimed to assay the frequency of CD4+CD25+ T cells in GD patients and to investigate the role of CD137-mediated costimulation in CD4+CD25+ T cells. METHODS: The frequencies of the CD4+CD25+ T cells in the peripheral blood (PB) of GD patients were determined by flow cytometric analysis. After the CD4+CD25+ T cells were isolated from PB mononuclear cells (PBMC) of the GD patients using immunomagnetic beads, the functional activity of the CD4+CD25+ T cells was characterized by use of a proliferation assay. mRNA expression of Foxp 3 in the CD4+CD25+ T cells of the GD patients was observed by real-time RT-PCR. RESULTS: In this study, we found that GD patients had a low proportion of CD4+CD25+ T cells (mean +/- SD; 1.47 +/- 0.31%) in PBMC as compared with normal subjects. CD137-mediated costimulation increased the expression of CD25 and Foxp 3 in CD4+ T cells in GD patients as compared with normal subjects. Moreover, the CD137-mediated costimulation also induced the proliferation of CD4+CD25+ T cells in GD patients, and the expanded CD4+CD25+ T cells could suppress other CD4+CD25- T cells in a co-culture. CONCLUSION: These results suggest that the peripheral expansion of CD4+CD25+ T cells by CD137-mediated co-stimulation can suppress effector T cells and may be a potent therapy for Graves' disease.
Key Words: CD137-mediated costimulation, CD4+CD25+ T cells, Foxp 3, Graves' disease, Peripheral blood mononuclear cells
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