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Original Article Expression of 4-1BB and 4-1BBL in Graves'Disease.
Eun Sook Kim, Hyo Won Jung, Il Sung Nam-Goong, Soon Joo Woo, Jung Il Choi, Young Il Kim
Endocrinology and Metabolism 2006;21(2):116-124
DOI: https://doi.org/10.3803/jkes.2006.21.2.116
Published online: April 1, 2006
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1Department of Internal Medicine, Ulsan University Hospital, College of Medicine, Korea.
2Biomedical Research Center, Ulsan University Hospital, Korea.

BACKGROUND
4-1BB mediated costimulatory signal is a recently identified immunotherapeutic strategy for treating autoimmune diseases without depressing the immune response. In this study, we investigated the expression of 4-1BB and 4-1BBL on the peripheral blood mononuclear cells (PBMC) and we assessed whether the serum levels of soluble (s) 4-1BB and s4-1BBL in the patients with Graves' disease (GD) and compared them with normal subjects. METHODS: Expression of 4-1BB and 4-1BBL on PBMC of GD patients was determined by flow cytometry. The concentrations of s4-1BB and s4-1BBL were assessed in the sera of GD patients by performing ELISA. RESULTS: 4-1BB was constitutively expressed on naive CD4+ and CD8+ T cells of the GD patients and this was increased by stimulation. 4-1BBL was also expressed on the antigen-presenting cells such as CD19+ B cells, monocytes and dendritic cells in GD patients. The serum levels of s4-1BB and s4-1BBL were significantly higher in GD patients than those in controls, and these levels were significantly correlated with the serum levels of thyroid-binding inhibitory immunoglobulin and free T4. CONCLUSION: These results indicate that effector T cells of GD patients can be activated through the 4-1BB-mediated costimulatory signal. Elevated s4-1BB and s4-1BBL levels in the sera of GD patients may affect modulation of the clinical course in GD patients.

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