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Dendritic Cells Recruitment and In Vivo Priming of CD8⁺ CTL Induced by a Single Topical or Transepithelial Immunization Via the Buccal Mucosa with Measles Virus Nucleoprotein¹

Nathalie Etchart^2,*, Pierre-Olivier Desmoulins^*, Karine Chemin^*, Charles Maliszewski, Bertrand Dubois^*, Fabian Wild^* and Dominique Kaiserlian^3,*

^* Institut National de la Santé et de la Recherche Médical, Unité 404, Immunité et Vaccination, Lyon, France; and Immunex Corporation, Seattle, WA 98101

The buccal mucosa, a prototype of pluristratified mucosal epithelia, contains a network of directly accessible class II⁺ epithelial dendritic cells (DC), similar to skin Langerhans cells. We showed that a single buccal immunization with measles virus nucleoprotein (NP), by either topical application onto or intradermal injection in the buccal mucosa, induced in vivo priming of protective class I-restricted specific CD8⁺ CTL. Both routes of immunization with NP induced a rapid recruitment of DC into the mucosa, which peaked at 2 h and decreased by 24 h. Treatment of mice with Flt3 ligand resulted in an increased number of DC in the buccal mucosa and enhanced the frequency of IFN--producing NP-specific effectors and the NP-specific CTL response generated after buccal immunization with NP. Finally, NP-pulsed bone marrow-derived DC induced NP-specific IFN--producing cells upon adoptive transfer to naive mice. These data demonstrate that a viral protein delivered to DC of the buccal mucosa induces in vivo priming of protective anti-viral CD8⁺ CTL.

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