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T. Sumi, A. Fukushima, K. Fukuda, N. Kumagai, T. Nishida, M. Azuma, H. Yagita, H. Ueno; Roles of Co-Stimulatory Molecules in the Development of Murine Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5204.
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© ARVO (1962-2015); The Authors (2016-present)
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) and 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 (4-1BB, 4-1BB ligand (L), OX40, OX40L, inducible costimulator (ICOS), B7-related protein 1 (B7RP-1), programmed death-1 (PD-1), PD-L1, PD-L2, B7-1, B7-2 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)) were injected into EC-developing mice either during the induction or the effector phase.
During the induction phase, treatment with anti-4-1BB Ab, anti-OX40L Ab or combination of anti-B7-1 and anti-B7-2 Abs suppressed EC, while anti-OX40 Ab or anti-CTLA-4 Ab treatment augmented EC. During the effector phase, treatment with anti-4-1BB Ab, anti-PD-L2 Ab or anti-B7-2 Ab suppressed EC. Treatment with other Abs as described above did not significantly affect EC.
These results demonstrated that each co-stimulatory molecule differently participates in the development of EC. In addition, co-stimulatory molecules within TNF-receptor family molecules play more significant roles than those within B7 family molecules, although treatment with Abs against co-stimulatory molecules of each family significantly affected systemic immune responses.
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