Send to

Choose Destination
Mucosal Immunol. 2018 Jan;11(1):273-289. doi: 10.1038/mi.2017.14. Epub 2017 Mar 1.

M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection.

Author information

Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Medical Biotechnology Center, VIB and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.


Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-Ad restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection. Indeed, immunized IL-17A-/- mice were significantly less well protected compared with wild-type mice despite exhibiting comparable antibody levels. Similarly, poor protection was also observed in congenic Balb/B (H-2b) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69+ CD103low M2e-specific memory CD4 T cells were αβ TCR+ and 50% were Th17 cells that were associated with an early influx of neutrophils after virus challenge. Adoptively transferred M2e memory CD4 T cells were strong helper T cells, which accelerated M2e- but more importantly also hemagglutinin-specific IgG production. Thus, for the first time we demonstrate that M2e-specific memory CD4 T cells are broadly protective.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center