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Updated: Sep 4, 2025
Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study
Tim K Tsang1,2, Kwok-Tai Lam3, Yinping Liu3
1WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, Special Administrative Region, China.
Background:
The protective effect of T cell-mediated immunity against influenza virus infections in natural settings remains unclear, especially in seasonal epidemics.
Methods:
To explore the potential of such protection, we analyzed the blood samples collected longitudinally in a community-based study and covered the first wave of pandemic H1N1 (pH1N1), two subsequent pH1N1 epidemics, and three seasonal H3N2 influenza A epidemics (H3N2) for which we measured pre-existing influenza virus-specific CD4 and CD8 T cell responses by intracellular IFN-γ staining assay for 965 whole blood samples.
Results:
Based on logistic regression, we found that higher pre-existing influenza virus-specific CD4 and CD8 T cell responses were associated with lower infection odds for corresponding subtypes. Every fold increase in H3N2-specific CD4 and CD8 T cells was associated with 28% (95% CI 8%, 44%) and 26% (95% CI 8%, 41%) lower H3N2 infection odds, respectively. Every fold increase in pre-existing seasonal H1N1 influenza A virus (sH1N1)-specific CD4 and CD8 T cells was associated with 28% (95% CI 11%, 41%) and 22% (95% CI 8%, 33%) lower pH1N1 infection odds, respectively. We observed the same associations for individuals with pre-epidemic hemagglutination inhibition (HAI) titers < 40. There was no correlation between pre-existing influenza virus-specific CD4 and CD8 T cell response and HAI titer.
Conclusions:
We demonstrated homosubtypic and cross-strain protection against influenza infections was associated with T cell response, especially CD4 T cell response. These protections were independent of the protection associated with HAI titer. Therefore, T cell response could be an assessment of individual and population immunity for future epidemics and pandemics, in addition to using HAI titer.
