| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
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.
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