tetano
Editor, Senior Moderator
Mucosal Immunol. 2017 Mar 15. doi: 10.1038/mi.2017.14. [Epub ahead of print]
[h=1]M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection.[/h] Eliasson DG[SUP]1[/SUP], Omokanye A[SUP]1[/SUP], Sch?n K[SUP]1[/SUP], Wenzel UA[SUP]1[/SUP], Bernasconi V[SUP]1[/SUP], Bemark M[SUP]1[/SUP], Kolpe A[SUP]2[/SUP], El Bakkouri K[SUP]2[/SUP], Ysenbaert T[SUP]2[/SUP], Deng L[SUP]2[/SUP], Fiers W[SUP]2[/SUP], Saelens X[SUP]2[/SUP], Lycke N[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-A[SUP]d[/SUP] 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[SUP]-/-[/SUP] 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-2[SUP]b[/SUP]) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69[SUP]+[/SUP] CD103[SUP]low[/SUP] M2e-specific memory CD4 T cells were αβ TCR[SUP]+[/SUP] 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.Mucosal Immunology advance online publication 15 March 2017. doi:10.1038/mi.2017.14.
PMID: 28295019 DOI: 10.1038/mi.2017.14
[h=1]M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection.[/h] Eliasson DG[SUP]1[/SUP], Omokanye A[SUP]1[/SUP], Sch?n K[SUP]1[/SUP], Wenzel UA[SUP]1[/SUP], Bernasconi V[SUP]1[/SUP], Bemark M[SUP]1[/SUP], Kolpe A[SUP]2[/SUP], El Bakkouri K[SUP]2[/SUP], Ysenbaert T[SUP]2[/SUP], Deng L[SUP]2[/SUP], Fiers W[SUP]2[/SUP], Saelens X[SUP]2[/SUP], Lycke N[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-A[SUP]d[/SUP] 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[SUP]-/-[/SUP] 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-2[SUP]b[/SUP]) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69[SUP]+[/SUP] CD103[SUP]low[/SUP] M2e-specific memory CD4 T cells were αβ TCR[SUP]+[/SUP] 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.Mucosal Immunology advance online publication 15 March 2017. doi:10.1038/mi.2017.14.
PMID: 28295019 DOI: 10.1038/mi.2017.14