Anti-T cell immunoglobulin and mucin domain-2 monoclonal antibody exacerbates collagen-induced arthritis by stimulating B cells.
Anti-T cell immunoglobulin and mucin domain-2 monoclonal antibody exacerbates collagen-induced arthritis by stimulating B cells.
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DOI：
10.1186/ar3288
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发表时间：
2011-03-22
影响因子：
4.9
通讯作者：
Akiba H
中科院分区：
文献类型：
--
作者：
Kawamoto T;Abe Y;Ito J;Makino F;Kojima Y;Usui Y;Ma J;Morimoto S;Yagita H;Okumura K;Takasaki Y;Akiba H
T细胞免疫球蛋白和粘蛋白结构域-2（TIM-2）已显示调节CD 4 T细胞活化。然而，TIM-2在自身免疫性疾病模型中的作用尚未阐明。在这项研究中，我们研究了抗TIM-2单克隆抗体（mAb）在胶原诱导性关节炎（CIA）中的作用，以确定TIM-2是否有助于T辅助细胞（Th）1或Th 17细胞的发展和关节炎症。在CIA的早期或晚期阶段用抗TIM-2 mAb治疗DBA/1小鼠。从淋巴结细胞培养物中评估II型胶原（CII）特异性CD 4 T细胞增殖反应和细胞因子产生。ELISA法检测血清中CII特异性抗体水平。流式细胞术检测CD 4 T细胞和B细胞表面TIM-2的表达。在早期阶段而不是晚期阶段施用抗TIM-2 mAb显著加剧了CIA的发展。尽管抗TIM-2单克隆抗体治疗不影响引流淋巴结中Th 1或Th 17细胞的发育，但抗TIM-2治疗小鼠中抗CII抗体的血清水平显著增加。TIM-2表达在脾B细胞上，并且通过抗免疫球蛋白（IG）M、抗CD 40和白细胞介素（IL）-4刺激进一步上调。相反，即使用抗-CD 3和抗-CD 28 mAb刺激，CD 4 T细胞也不表达TIM-2。有趣的是，抗TIM-2单克隆抗体在体外增强活化的B细胞的增殖和抗体产生。TIM-2信号在CIA早期影响B细胞的增殖和抗体产生，但不影响Th 1或Th 17细胞的诱导。
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. 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. 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. 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.
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