J Korean Soc Endocrinol.  2006 Apr;21(2):116-124. 10.3803/jkes.2006.21.2.116.

Expression of 4-1BB and 4-1BBL in Graves'Disease

• Kim ES
• Jung HW
• Nam-Goong
• Woo SJ
• Choi JI
• Kim YI

• KMID: 1511950
• DOI: http://doi.org/10.3803/jkes.2006.21.2.116

Abstract

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.

MeSH Terms

Antigen-Presenting Cells
Autoimmune Diseases
B-Lymphocytes
Dendritic Cells
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Graves Disease
Humans
Immunoglobulins
Monocytes
T-Lymphocytes
Immunoglobulins

Figure

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  Fig. 1. Expression levels of 4-1BB and 4-1BBL on PBMC of the patients with Graves’ disease (GD). Naïve PBMC were activated with 1 μg/mL of anti-CD3 mAb and 5 μg/mL of LPS for 24 hr. Expression levels of 4-1BB (A) and 4-1BBL (B) on PBMC of patients with GD were analyzed by flow cytometry compared with control group.

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  Fig. 2. Expression patterns of 4-1BB and 4-1BBL on PBMC of the patients with Graves’ disease. A and C, PE conjugated CD4+/CD8+ T cells with FITC conjugated 4-1BB/4-1BBL fluorescence dot plots in the lymphocytes population of PBMC with healthy subject (A) and GD patient (C) by two-color cytometry. Square box presents double-positive cell population. B and D, 4-1BBL expression on primary monocytes (Mo) and monocyte-derived dendritic cells (DCs) of healthy subject (B) and GD patient (D) by single-color flow cytometric histogram. The thick lines represent 4-1BBL+ cells and the thin lines represent isotype-matched mAb as a control.

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  Fig. 3. Serum levels of s4-1BB and s4-1BBL in the patients with Graves’ disease. s4-1BB (A) and s4-1BBL (B) were assessed in sera of the patients with Graves’ disease by ELISA and compared with normal subjects as a control.

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  Fig. 4. Correlation between s4-1BB and s4-1BBL levels in sera of the patients with Graves’ disease. The concentrations of s4-1BB and s4-1BBL were measured in sera of the same patients by ELISA.

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  Fig. 5. Correlation between s4-1BB/s4-1BBL and clinical parameters of the patients with Graves’ disease (GD). A, Correlation between s4-1BB and TBII (%) levels in sera of the patients with GD. B, Correlation between s4-1BB and free T4 (ng/mL) levels in sera of GD patients. C, Correlation between s4-1BBL and TBII levels in sera of GD patients. D, Correlation between s4-1BBL and free T4 levels in sera of GD patients.

Reference

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