Mechanism of NKT cell activation by intranasal coadministration of α-galactosylceramide, which can induce cross-protection against influenza viruses

• Published in: Mucosal immunology Vol. 1; no. 3; pp. 208 - 218
• Main Authors: Kamijuku, H, Nagata, Y, Jiang, X, Ichinohe, T, Tashiro, T, Mori, K, Taniguchi, M, Hase, K, Ohno, H, Shimaoka, T, Yonehara, S, Odagiri, T, Tashiro, M, Sata, T, Hasegawa, H, Seino, K-i
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2008
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; Allergology; Animals; Antibodies; Antibody Specificity; Biomedicine; Chemokine CXCL16; Chemokine CXCL6 - immunology; Cross Reactions; Dendritic Cells - drug effects; Dendritic Cells - immunology; Fluorescent Dyes; Galactosylceramides - administration & dosage; Gastroenterology; Humans; Immunoglobulin A - biosynthesis; Immunoglobulin A - immunology; Immunology; Influenza A virus - immunology; Influenza A Virus, H5N1 Subtype - immunology; Influenza B virus - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Interleukin-4 - immunology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Nasal Mucosa - immunology; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Receptors, CXCR - immunology; Receptors, CXCR6; Vaccination - methods
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2008.2

In a nasal vaccine against influenza, the activation of natural killer T (NKT) cells by intranasal coadministration of α-galactosylceramide (α-GalCer) can potently enhance protective immune responses. The results of this study show that the NKT cell-activated nasal vaccine can induce an effective cross-protection against different strains of influenza virus, including H5 type. To analyze the mechanism of NKT cell activation by this nasal vaccine, we prepared fluorescence-labeled α-GalCer by which we detect a direct interaction between NKT cells and α-GalCer-stored dendritic cells in nasal mucosa-associated tissues. Accordingly, although very few NKT cells exist at mucosa, the nasal vaccination induced a localized increase in NKT cell population, which is partly dependent on CXCL16/CXCR6. Furthermore, we found that NKT cell activation stimulates mucosal IgA production by a mechanism that is dependent on interleukin (IL)-4 production. These results strengthen the basis of nasal vaccination via NKT cell activation, which can induce immune cross-protection.