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.


The Role for TIM-2 in Collagen-Induced Arthritis.

Kawamoto2,  Toshio, Akiba1,  Hisaya, Abe2,  Yoshiyuki, Morimoto2,  Shinji, Yamaji2,  Ken, Tamura2,  Naoto, Takasaki2,  Yoshinari

Department of Immunology, Juntendo University School of Medicine
Department of Rheumatology Juntendo University School of Medicine

Introduction:

T cell Ig and mucin domain-2 (TIM-2) has been shown to regulate CD4 T cell activation. TIM-2-deficient mice developed more severe airway inflammation under Th2-polarizing condition.Thus, it seems likely that TIM-2 is a negative regulator of Th2 immune responses. However, the immunological function of TIM-2 under Th1-polarizing condition is still unclear. This study therefore examined the contribution of TIM-2 to the development of collage typeII (CII)-induced arthritis (CIA), which is a Th1-polarized disease model, by administering a newly generated anti-TIM-2 mAb.

Methods:

In this study, we investigated the effects of anti-TIM-2 monoclonal antibodies in a collagen-induced arthritis (CIA), which is a mouse model of rheumatoid arthritis, to determine whether TIM-2 contributes to the development of pathogenic Th1 or Th17 cells and joint inflammation. A murine model of CIA can be induced by injection of CII emulsified with adjuvant in genetically susceptible DBA/1 mice. Mice were examined daily for the onset of CIA. The swelling of four paws was graded from 0 to 4,each paw was graded, and the four scores were totaled so that the maximal score per mouse was 16. Draining lymph node cells were isolated and pooled, and cultured in the presence or absence of indicated dose of denatured bovine CII. All cultures were pulsed with 3H-thymidine for the last 6h of a 72h or 96h culture and harvested. To determine the production of cytokines, cell-free supernatants were collected at 72h or 120h and assayed for INF-g or IL-17 were measured by ELISA. Serums were collected and titers of anti-CII IgG Abs were measured by ELISA.

Results:

Administration of anti-TIM-2 mAbs in early phase, but not late phase, significantly exacerbated the development of CIA. Although anti-TIM-2 mAbs treatment did not affect the development of Th1 or Th17 cells in the draining lymph node, the serum levels of anti-type II collagen Abs were significantly increased in the anti-TIM-2 mice. TIM-2 expression was found on splenic B cells and further up-regulated by anti-IgM, anti-CD40, and IL-4 stimulation. In contrast, CD4 T cells did not express TIM-2 even when stimulated with both anti-CD30 and anti-CD28 mAbs. Intrestingly, anti-TIM-2 mAbs enhanced proliferation and Ig production of activated B cells in vitro.

Conclusions:

These results suggest that the exacerbation of CIA by anti-TIM-2 mAbs is caused by enhancement of B cell activation and Ab production.

To cite this abstract, please use the following information:
Kawamoto, Toshio, Akiba, Hisaya, Abe, Yoshiyuki, Morimoto, Shinji, Yamaji, Ken, Tamura, Naoto, et al; The Role for TIM-2 in Collagen-Induced Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1731
DOI: 10.1002/art.29496

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