title: Protective neutralizing influenza antibody response in the absence of T follicular helper cells.
abstract: Virus infection induces the development of T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFHcells are important in anti-viral humoral immunity, the contribution of TH1 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 TFHcells and germinal centers. The cytokines interleukin-21 and interferon-γ, which are secreted from TH1 cells, were essential for the observed greater persistence and higher titers of IgG2 protective antibodies. Our results suggest that TH1 induction could be a promising strategy for producing effective neutralizing antibodies against emerging influenza viruses.
authors: Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Yokohama, Japan.
authors: Kosuke
authors: K
authors: Miyauchi
authors: Drug Discovery Antibody Platform Unit, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
authors: Akiko
authors: A
authors: Sugimoto-Ishige
authors: Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Noda, Japan.
authors: Yasuyo
authors: Y
authors: Harada
authors: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Yu
authors: Y
authors: Adachi
authors: Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Yokohama, Japan.
authors: Yoshiko
authors: Y
authors: Usami
authors: Drug Discovery Antibody Platform Unit, IMS, RIKEN Yokohama Institute, Yokohama, Japan.|Biological Research Department, Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Ltd, Tokyo, Japan.
authors: Tomohiro
authors: T
authors: Kaji
authors: Laboratory for Integrated Cellular Systems, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
authors: Kentaro
authors: K
authors: Inoue
authors: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Hideki
authors: H
authors: Hasegawa
authors: Laboratory for Integrative Genomics, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
authors: Takashi
authors: T
authors: Watanabe
authors: Department of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Japan.
authors: Atsushi
authors: A
authors: Hijikata
authors: Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.|Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: Satoshi
authors: S
authors: Fukuyama
authors: Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors: Tadashi
authors: T
authors: Maemura
authors: Laboratory for Integrated Cellular Systems, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
authors: Mariko
authors: M
authors: Okada-Hatakeyama
authors: Laboratory for Integrative Genomics, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
authors: Osamu
authors: O
authors: Ohara
authors: Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.|Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, USA.|ERATO Infection-induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan.
authors: Yoshihiro
authors: Y
authors: Kawaoka
authors: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Yoshimasa
authors: Y
authors: Takahashi
authors: Drug Discovery Antibody Platform Unit, IMS, RIKEN Yokohama Institute, Yokohama, Japan.
authors: Toshitada
authors: T
authors: Takemori
authors: Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Yokohama, Japan.|Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Noda, Japan.
authors: Masato
authors: M
authors: Kubo
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D007378:Interleukins; D007371:Interferon-gamma; D000098546:Interleukin-21