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,
* Mucosal Immunology Section and
Laboratory Science Division, International Vaccine Institute, Seoul, Korea; and
Institut National de la Santé et de la Recherche Médicale Unité 721, Faculté de Médecine de Nice, Nice, France
Our previous studies demonstrated the potential of the sublingual (s.l.) route for delivering vaccines capable of inducing mucosal as well as systemic immune responses. Those findings prompted us to attempt to identify possible inductive mechanism of s.l. vaccination for immune responses. Within 2 h after s.l. administration with cholera toxin (CT), significantly higher numbers of MHC class II+ cells accumulated in the s.l. mucosa. Of note, there were brisk expression levels of both CCL19 and CCL21 in cervical lymph nodes (CLN) 24 h after s.l. vaccination with CT. In reconstitution experiments using OVA-specific CD4+ or CD8+ T cells, s.l. vaccination elicited strong Ag-specific T cell proliferation mainly in CLN. Interestingly, Ag-specific T cell proliferation completely disappeared in CD11c-depleted and CCR7–/– mice but not in Langerin-depleted, macrophage-depleted, and CCR6–/– mice. Similar to CD4+ T cell responses, induction of Ag-specific IgG (systemic) and IgA (mucosal) Ab responses were significantly reduced in CD11c-depleted and CCR7–/– mice after s.l. vaccination with OVA plus CT. Although CD8
– dendritic cells ferried Ag from the s.l. mucosa, both migratory CD8– and resident CD8+ dendritic cells were essential to prime CD4+ T cells in the CLN. On the basis of these findings, we believe that CCR7 expressed CD8–CD11c+ cells ferry Ag in the s.l. mucosa, migrate into the CLN, and share the Ag with resident CD8+CD11c+ cells for the initiation of Ag-specific T and B cell responses following s.l. challenge. We propose that the s.l. mucosa is one of the effective mucosal inductive sites regulated by the CCR7-CCL19/CCL21 pathway.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This was supported by the governments of the Republic of Korea, Sweden, and Kuwait and a Korea Science and the Korean Ministry of Science and Technology, and Regional Technology Innovation Program of the Ministry of Commerce, Industry, and Energy (RT104-01-01).
2 Address correspondence and reprint requests to Dr. Mi-Na Kweon, Mucosal Immunology Section, International Vaccine Institute, Seoul National University Research Park, Kwanak-Gu, Seoul, 151-818 Korea. E-mail address: mnkweon{at}ivi.int
3 Abbreviations used in this paper: s.l., sublingual; BW, body weight; CLN, cervical lymph node; CT, cholera toxin; CTB, CT subunit B; DAPI, 4',6-diamidino-2-phenylindole; DC, dendritic cell; DT, diphtheria toxin; FAE, follicle-associated epithelium; HA, hemagglutinin; LC, Langerhans cell; LN, lymph node; LP, lamina propria.
4 The online version of this article contains supplemental material.
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