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Original Article 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
Endocrinology and Metabolism 2007;22(5):332-338
DOI: https://doi.org/10.3803/jkes.2007.22.5.332
Published online: October 1, 2007
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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.
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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.

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