Anti-T cell immunoglobulin and mucin domain-2 monoclonal antibody exacerbates collagen-induced arthritis by stimulating B cells.

Abstract

INTRODUCTION:

T cell immunoglobulin and mucin domain-2 (TIM-2) has been shown to regulate CD4 T cell activation. However, the role of TIM-2 in the autoimmune disease models has not been clarified yet. In this study, we investigated the effects of anti-TIM-2 monoclonal antibodies (mAbs) in collagen-induced arthritis (CIA) to determine whether TIM-2 contributes to the development of T helper (Th) 1 or Th17 cells and joint inflammation.

METHODS:

DBA/1 mice were treated with anti-TIM-2 mAbs during the early or late phase of CIA. Type II collagen (CII)-specific CD4 T-cell proliferative response and cytokine production were assessed from lymph node cell culture. The serum levels of CII-specific antibody were measured by ELISA. The expression of TIM-2 on CD4 T cells or B cells was determined by flow cytometric analysis.

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-CII antibodies were significantly increased in the anti-TIM-2-treated mice. TIM-2 expression was found on splenic B cells and further up-regulated by anti-immunoglobulin (Ig)M, anti-CD40, and interleukin(IL)-4 stimulation. In contrast, CD4 T cells did not express TIM-2 even when stimulated with both anti-CD3 and anti-CD28 mAbs. Interestingly, anti-TIM-2 mAbs enhanced proliferation and antibody production of activated B cells in vitro.

CONCLUSIONS:

TIM-2 signaling influences both proliferation and antibody production of B cells during the early phase of CIA, but not induction of Th1 or Th17 cells.

• Authors: Toshio Kawamoto, Yoshiyuki Abe, Jun Ito, Fumihiko Makino, Yuko Kojima, Yoshihiko Usui, Juan Ma, Shinji Morimoto, Hideo Yagita, Ko Okumura, Yoshinari Takasaki, Hisaya Akiba
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 13 Issue 2 Pg. R47 (Mar 22 2011) ISSN: 1478-6362 [Electronic] England
• PMID: 21426565 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Membrane Proteins
• Timd2 protein, mouse

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Arthritis, Experimental (immunology, metabolism)
• B-Lymphocytes (immunology, metabolism)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cell Proliferation
• Cell Separation
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Immunoprecipitation
• Lymphocyte Activation (immunology)
• Male
• Membrane Proteins (immunology, metabolism)
• Mice
• Mice, Inbred DBA
• Rats
• Rats, Sprague-Dawley