2006 Fiscal Year Final Research Report Summary
Roles of co-stimulatory molecules in the development of murine allergic conjunctivitis
| Project/Area Number |
17591838
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Kochi University |
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Principal Investigator |
FUKUSHIMA Atsuki Kochi University, medical department, associate professor, 医学部, 助教授 (40281737)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Allergic Conjunctival Disease / T cell / Co-stimulatory Molecule / Adhesion Molecule / 4-1BB / OX40 / VLA-4 / VCAM-2 |
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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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