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A. B. Nesburn, A. A. Chentoufi, G. Dasgupta, I. Bettahi, N. R. Binder, Z. S. Choudhury, W. D. Chamberlain, S. L. Wechsler, L. BenMohamed; Nasolacrimal Duct Closure Modulates Ocular Mucosal and Systemic CD4+ T Cell Responses Induced Following Topical Ocular or Intranasal Immunization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1572.
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Both topical ocular and topical intranasal immunizations have been reported to stimulate the ocular mucosal immune system (OMIS) and the systemic immune system. Nasolacrimal ducts (NLDs) are the connecting bridges between OMIS and nasal associated lymphoid tissue (NALT). These ducts drain topical ocular administrated solutions into the inferior meatus of the nose to reach the NALT. Inversely, NLDs also drain intranasally administrated solutions to the mucosal surface of eye and thus the OMIS. This unique anatomical connection between the OMIS and NALT systems provoked us to test whether OMIS and NALT are immunologically interdependent.
CD4+ T cell epitope peptides from HSV-1 glycoprotein D (gD) emulsified with the mucosal adjuvant CpG2007 were used to immunize rabbits either ocularly or intranasally. In some rabbits the ocular and intranasal compartments were isolated by surgical closure of NLDs.
Topical ocular and topical intranasal administration of the vaccine induced local (conjunctival) as well as systemic (spleenic) HSV-peptide-specific CD4+ T cell responses. Topical ocular immunization in rabbits with sealed NLDs induced local ocular mucosal CD4+ T cell responses similar to those induced in normal rabbits, while systemic CD4+ T cell responses were significantly increased (as measured by T cell proliferation and IFN-γ production; p < 0.005). In contrast, topical intranasal immunization in rabbits with sealed NLDs induced systemic CD4+ T cell responses similar to those induced in normal rabbits, while ocular mucosal immune responses were significantly decreased (p < 0.001).
These studies confirm that both topical ocular and topical intranasal administration of HSV-1 epitopes can induce local and systemic immune responses. In addition, the results suggest that NALT and OMIS are immunologically interconnected.
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