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

H Kamijuku; Y Nagata; X Jiang; T Ichinohe; T Tashiro; K Mori; M Taniguchi; K Hase; H Ohno; T Shimaoka; S Yonehara; T Odagiri; M Tashiro; T Sata; H Hasegawa; K-i Seino

doi:10.1038/mi.2008.2

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

Mucosal Immunol. 2008 May;1(3):208-18. doi: 10.1038/mi.2008.2. Epub 2008 Mar 5.

Authors

H Kamijuku¹, Y Nagata, X Jiang, T Ichinohe, T Tashiro, K Mori, M Taniguchi, K Hase, H Ohno, T Shimaoka, S Yonehara, T Odagiri, M Tashiro, T Sata, H Hasegawa, K-i Seino

Affiliation

¹ Division of Bioregulation Research, Institute of Medical Science, St Marianna University School of Medicine, Miyamae-ku, Kawasaki City, Kanagawa, Japan.

PMID: 19079180
DOI: 10.1038/mi.2008.2

Abstract

In a nasal vaccine against influenza, the activation of natural killer T (NKT) cells by intranasal coadministration of alpha-galactosylceramide (alpha-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 alpha-GalCer by which we detect a direct interaction between NKT cells and alpha-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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / administration & dosage*
Administration, Intranasal
Animals
Antibody Specificity
Chemokine CXCL16
Chemokine CXCL6 / immunology
Cross Reactions
Dendritic Cells / drug effects
Dendritic Cells / immunology
Fluorescent Dyes
Galactosylceramides / administration & dosage*
Humans
Immunoglobulin A / biosynthesis
Immunoglobulin A / immunology
Influenza A Virus, H5N1 Subtype / immunology
Influenza A virus / 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*

Substances

Adjuvants, Immunologic
Chemokine CXCL16
Chemokine CXCL6
Cxcl16 protein, mouse
Cxcr6 protein, mouse
Fluorescent Dyes
Galactosylceramides
Immunoglobulin A
Influenza Vaccines
Receptors, CXCR
Receptors, CXCR6
alpha-galactosylceramide
Interleukin-4