Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Underexpression of TIM-3 and Blunted Galectin-372-Induced Apoptosis of CD4 T Cells in Rheumatoid Arthritis.

Lee4,  Jaejoon, Oh6,  Ji-Min, Hwang6,  Ji Won, Park6,  Eun-Jung, Bae3,  Eun-Kyung, Ahn1,  Joong Kyong, Lee2,  Yoo Sun

Kangbook Samsung Hospital, Sungkyunkwan University School of Medicine
Masan Samsung Hospital, Sungkyunkwan University School of Medicine
Samsung Biomedical Research Institute
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of
Samsung Medical Center, Sungkyunkwan University School of Medicine

Purpose:

T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is a novel transmembrane protein involved in the negative regulation of Th1 cell-mediated immunity by interacting with its ligand galectin-9. Galectin-9 has been shown to induce apoptosis of TIM-3 expressing Th1 cells in vitro and in vivo. We have previously demonstrated that, in rheumatoid arthritis (RA) patients, TIM-3 is expressed in the synovial tissues and that TIM-3 mRNA expression in the peripheral mononuclear cells is inversely correlated with disease activity as measured by DAS28. We hypothesize that galectin-9 induced apoptosis of Th1 cells in RA is impaired because of aberrantly low TIM-3 expression which may lead to augmented Th1 response. This study was therefore undertaken to investigate the expression of TIM-3 from CD4+ T cells and galectin-372-mediated apoptosis of CD4+T cells from RA patients and healthy controls.

Methods:

CD4+T cells from RA patients and healthy controls were isolated from peripheral blood mononuclear cells and then were activated. The expression of TIM-3 mRNA in CD4+T cells was measured using real-time PCR. After CD4+T cells were activated in the presence of graded doses of galectin-9 or control, galectin-9 induced cytotoxicity and apoptotic activity of CD4+ T cells were analyzed using MTT assays and annexin V staining, respectively.

Results:

TIM-3 mRNA expression was significantly lower in CD4+T cells from RA patients compared to those in healthy controls (p=0.028). CD4+T cell survival as measured by MTT assay when incubated with galectin-9 (15nM) was significantly higher in RA patients than in healthy controls (p=0.002). The increased survival trend of CD4+ T cells from RA patients was maintained at higher dose of galectin-9 (50nM), but did not reach statistical significance (p=0.078). Apoptotic activity of CD4+ cells from healthy controls as measured by annexin V staining increased with graded doses of galectin-9 (0nM vs. 30nM, 0nM vs. 90nM, p=0.016 each). However, apoptotic activity of CD4+T cells from RA patients did not change despite the stimulation with galectin-9.

Conclusion:

Galectin-372-mediated apoptosis of CD4+ T cells is dysfunctional in RA patients. Blunted galectin-372-mediated apoptosis may be exerted through underexpression of TIM-3 that negatively regulates Th1 response. Our data suggest that TIM-3 and its interaction with galectin-9 may play an important role in the pathogenesis of RA and may represent a potential therapeutic target.

To cite this abstract, please use the following information:
Lee, Jaejoon, Oh, Ji-Min, Hwang, Ji Won, Park, Eun-Jung, Bae, Eun-Kyung, Ahn, Joong Kyong, et al; Underexpression of TIM-3 and Blunted Galectin-372-Induced Apoptosis of CD4 T Cells in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :372
DOI: 10.1002/art.28141

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