Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction

J Infect Dis. 2020 Jan 1;221(1):21-32. doi: 10.1093/infdis/jiz321.


Background: Influenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown.

Methods: We collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay.

Results: We report that LAIV induced early (3-7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV.

Conclusions: Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.

Keywords: LAIV; TFH cells; antibody responses; influenza; tonsils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antibodies, Viral / blood*
  • Child
  • Child, Preschool
  • Humans
  • Immunogenicity, Vaccine*
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / metabolism
  • Influenza B virus / immunology
  • Influenza Vaccines / immunology*
  • Middle Aged
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology*
  • Saliva / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Time Factors
  • Vaccination
  • Vaccines, Attenuated
  • Young Adult


  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • Influenza Vaccines
  • Vaccines, Attenuated