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BMC Med . Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study

tetano

Editor, Senior Moderator
BMC Med


. 2022 Jul 21;20(1):230.
doi: 10.1186/s12916-022-02429-7.
Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study


Tim K Tsang[SUP] 1 2 [/SUP], Kwok-Tai Lam[SUP] 3 [/SUP], Yinping Liu[SUP] 3 [/SUP], Vicky J Fang[SUP] 1 [/SUP], Xiaofeng Mu[SUP] 3 [/SUP], Nancy H L Leung[SUP] 1 2 [/SUP], J S Malik Peiris[SUP] 1 4 5 [/SUP], Gabriel M Leung[SUP] 1 2 [/SUP], Benjamin J Cowling[SUP] #[/SUP][SUP] 6 7 [/SUP], Wenwei Tu[SUP] #[/SUP][SUP] 8 [/SUP]



Affiliations

Abstract

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.

Keywords: Influenza; Susceptibility; T cell-mediated immunity.
 
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