Roles of co-stimulatory molecules in the development of murine allergic conjunctivitis

我们已经证明ag特异性T细胞在小鼠实验性过敏性结膜炎（EC）的发展中起主导作用。激活T细胞需要来自共刺激分子的信号。因此，我们旨在研究与t细胞活化相关的共刺激分子在EC的发展中所起的作用。在BALB/c小鼠中，采用豚草（RW）主动免疫或豚草诱导的脾细胞转移被动免疫，再用滴眼液刺激RW诱导EC。RW攻毒24小时后，取结膜进行组织学分析，测定结膜浸润性嗜酸性粒细胞数量。为了研究共刺激分子的作用，在诱导期和效应期向ec发育小鼠注射了抗共刺激分子的抗体（Abs）。在诱导阶段，抗4- 1bb Ab或抗ox40l Ab处理抑制EC，而抗ox40 Ab处理增强EC。在效应期，抗4- lbb抗体抑制EC，而抗b7dc抗体增强EC。相反，抗b7rp - 1抗体处理对EC无显著影响。这些结果表明，每种共刺激分子不同程度地参与了EC的发展。对于在嗜酸性粒细胞浸润中起重要作用的vla4和VCAM-1，通过诱导EC使vla4阳性细胞浸润到结膜内。阻断vca -4和VCAM-1均可抑制结膜嗜酸性粒细胞浸润。因此，vca -4和VCAM-1之间的相互作用在EC的发展中起着至关重要的作用。

We have demonstrated that Ag-specific T cells play a predominant role in the development of experimental allergic conjunctivitis (EC) in mice. Activation of T cells requires the signal from co-stimulatory molecules. Therefore, we aimed to investigate the roles of co-stimulatory molecules related to T-cell activation play in the development of EC. EC was induced in BALB/c mice by active immunization with ragweed (RW) or passive immunization by transfer of RW-primed splenocytes followed by RW challenge in eye drops. Twenty-four hours after the RW challenge, the conjunctivas were harvested for histological analysis to determine the conjunctival infiltrating eosinophil numbers. To investigate the involvement of co-stimulatory molecules, antibodies (Abs) against co-stimulatory molecules were injected into EC-developing mice either during the induction or the effector phase. During the induction phase, treatment with anti-4-1BB Ab or anti-OX40L Ab suppressed EC, while anti-OX40 Ab treatment augmented EC. During the effector phase, treatment with anti-4-lBB Ab suppressed EC, whereas treatment with anti-B7DC Ab augmented EC. On the contrary, treatment with anti-B7RP-l Ab did not significantly affect EC. These results demonstrate that each co-stimulatory molecule differently participates in the development of EC. With regard to VLA-4 and VCAM-1 which play an important role in eosinophil infiltration, VLA-4 positive cells infiltrated into the conjunctiva by the induction of EC. Blocking of both VLA-4 and VCAM-1 inhibited conjunctival eosinophil infiltration. Thus, the interaction between VLA-4 and VCAM-1 plays a critical role in the development of EC.