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.


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.

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*


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