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

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

Author information

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.

Abstract

Virus infection induces the development of T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFH cells 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 TFH cells 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.

PMID:
27798619
DOI:
10.1038/ni.3563
[Indexed for MEDLINE]

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