Protective neutralizing influenza antibody response in the absence of T follicular helper cells

Kosuke Miyauchi; Akiko Sugimoto-Ishige; Yasuyo Harada; Yu Adachi; Yoshiko Usami; Tomohiro Kaji; Kentaro Inoue; Hideki Hasegawa; Takashi Watanabe; Atsushi Hijikata; Satoshi Fukuyama; Tadashi Maemura; Mariko Okada-Hatakeyama; Osamu Ohara; Yoshihiro Kawaoka; Yoshimasa Takahashi; Toshitada Takemori; Masato Kubo

doi:10.1038/ni.3563

Protective neutralizing influenza antibody response in the absence of T follicular helper cells

Nat Immunol. 2016 Dec;17(12):1447-1458. doi: 10.1038/ni.3563. Epub 2016 Oct 31.

Authors

Kosuke Miyauchi¹, Akiko Sugimoto-Ishige², Yasuyo Harada³, Yu Adachi⁴, Yoshiko Usami¹, Tomohiro Kaji^{2

5}, Kentaro Inoue⁶, Hideki Hasegawa⁷, Takashi Watanabe⁸, Atsushi Hijikata⁹, Satoshi Fukuyama^{10

11}, Tadashi Maemura¹⁰, Mariko Okada-Hatakeyama⁶, Osamu Ohara⁸, Yoshihiro Kawaoka^{10

11

12}, Yoshimasa Takahashi⁴, Toshitada Takemori², Masato Kubo^{1

3}

Affiliations

¹ Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Yokohama, Japan.
² Drug Discovery Antibody Platform Unit, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
³ Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Noda, Japan.
⁴ Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
⁵ Biological Research Department, Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Ltd, Tokyo, Japan.
⁶ Laboratory for Integrated Cellular Systems, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
⁷ Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
⁸ Laboratory for Integrative Genomics, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
⁹ Department of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Japan.
¹⁰ Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
¹¹ Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹² ERATO Infection-induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan.

PMID: 27798619
DOI: 10.1038/ni.3563

Abstract

Virus infection induces the development of T follicular helper (T_FH) and T helper 1 (T_H1) cells. Although T_FH cells are important in anti-viral humoral immunity, the contribution of T_H1 cells to a protective antibody response remains unknown. We found that IgG2 antibodies predominated in the response to vaccination with inactivated influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAV strains, even in mice that lacked T_FH cells and germinal centers. The cytokines interleukin-21 and interferon-γ, which are secreted from T_H1 cells, were essential for the observed greater persistence and higher titers of IgG2 protective antibodies. Our results suggest that T_H1 induction could be a promising strategy for producing effective neutralizing antibodies against emerging influenza viruses.

MeSH terms

Animals
Antibodies, Neutralizing / blood
Antibodies, Viral / blood
Cells, Cultured
Germinal Center / immunology*
Humans
Immunoglobulin G / blood
Influenza A Virus, H1N1 Subtype / immunology*
Influenza A Virus, H5N1 Subtype / immunology*
Influenza Vaccines / immunology*
Influenza, Human / immunology*
Interferon-gamma / metabolism
Interleukins / genetics
Interleukins / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections / immunology*
Th1 Cells / immunology*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Immunoglobulin G
Influenza Vaccines
Interleukins
Interferon-gamma
interleukin-21