Engagement of 4-1BB inhibits the development of experimental allergic conjunctivitis in mice
Engagement of 4-1BB inhibits the development of experimental allergic conjunctivitis in mice
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DOI：
10.4049/jimmunol.175.8.4897
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发表时间：
2005-10-15
影响因子：
4.4
通讯作者：
Ueno, H
中科院分区：
文献类型：
--
作者：
Fukushima, A;Yamaguchi, T;Ueno, H
4-1BB受体在CD 8（+）T细胞活化中作为共刺激物。通过用抗4-1BB Ab处理通过该分子的激动性刺激已被证明抑制动物中的各种实验诱导的疾病。然而，抗4-1BB抗体对实验性变态反应性疾病的作用尚未见报道。我们研究了抗4-1BB抗体对小鼠实验性过敏性结膜炎发生和发展的影响。为了检查抗体在诱导或效应期的作用，用激动性抗4-1BB抗体、阻断性抗4 - 1BB配体抗体或正常大鼠IgG处理通过脾细胞转移主动免疫的小鼠或被动免疫的小鼠。在诱导期或效应期，抗4-1BB Ab治疗显著减少了野生型小鼠结膜中的嗜酸性粒细胞浸润。抗4-1BB All治疗显着减少了脾细胞产生的Th 2细胞因子和总血清IgE，而IFN-γ的产生增加。抗4-伊布Ab处理诱导脾脏中CD 8阳性细胞数量的相对增加。此外，在主动免疫的IFN-γ敲除小鼠中也注意到通过用抗4-1BB Ab治疗抑制嗜酸性粒细胞浸润。总之，在体内用激动性抗4-1BB抗体在诱导期或效应期治疗抑制实验性过敏性结膜炎的发展，并且这种抑制可能是通过抑制Th 2免疫应答而不是上调IFN-γ介导的。
The 4-1BB receptor acts as a costimulator in CD8(+) T cell activation. Agonistic stimulation through this molecule by treatment with anti-4-1BB Abs has been demonstrated to inhibit various experimentally induced diseases in animals. However, the effect of anti-4-1BB Abs on experimental allergic diseases has not been reported. We investigated the effect of anti-4-1BB Abs on the development and progression of experimental allergic conjunctivitis in mice. To examine the effects of Abs during the induction or effector phase, actively immunized mice or passively immunized mice by splenocyte transfer were treated with agonistic anti-4-1BB Abs, blocking anti-4-1BB ligand Abs, or normal rat IgG. Eosinophil infiltration into the conjunctiva was significantly reduced in wild-type mice by the anti-4-1BB Ab treatment during either induction or effector phase. Th2 cytokine production by splenocytes and total serum IgE were significantly reduced by the anti-4-1BB All treatment, while IFN-gamma production was increased. The anti-4-IBB Ab treatment induced a relative increase of CD8-positive cell numbers in the spleens. Moreover, inhibition of eosinophil infiltration by the treatment with anti-4-1BB Abs was also noted in actively immunized IFN-gamma knockout mice. Taken altogether, in vivo treatment with agonistic anti-4-1BB Abs in either induction or effector phase inhibits the development of experimental allergic conjunctivitis, and this inhibition is likely to be mediated by suppression of Th2 immune responses rather than up-regulation of IFN-gamma.