Differences in the influenza-specific CD4 T cell immunodominance hierarchy and functional potential between children and young adults

Studies of the B cell repertoire suggest that early childhood influenza infections profoundly shape later reactivity by creating an “imprint” that impacts subsequent vaccine responses and may provide lasting protection against influenza strains within the same viral group. However, there is little known about how these early childhood influenza exposures shape CD4 T cell reactivity later in life. To investigate the effect of age on influenza-specific CD4 T cell specificity and functionality, reactivity in cohorts of 2 year old children and young adult subjects was compared. Intracellular cytokine staining was used to determine the viral antigen specificity and expression levels of various cytokines following stimulation of peripheral blood mononuclear cells with complete peptide pools representing the entire translated sequences of the pH1, H3, HA-B, NP, and M1 proteins. We found that the influenza protein-specific immunodominance pattern in children differs from that in young adults, with much lower reactivity to the NP internal virion protein in young children. Alterations in CD4 T cell functionality were also noted, as responding CD4 T cells from children produced less IFNγ and were less likely to express multiple cytokines. These differences in the repertoire of influenza-specific CD4 T cells available for recall on influenza challenge in early childhood could possibly contribute to early imprinting of influenza-specific immunity as well as the increased susceptibility of children to this viral infection.