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Clonotypic analysis of protective influenza M2e-specific lung resident T helper memory cells reveals extensive functional plasticity

ABSTRACT: Intranasal influenza immunization with CTA1-3M2e-DD stimulated M2e-specific Th17 tissue resident memory (Trm) cells that conferred strong antibody-independent protection against infection at 6 months after priming. These cells rapidly expanded in the lung upon infection and effectively restricted virus replication. Single-cell RNAseq transcriptomic and TCR VDJ-analysis of M2e- tetramer-sorted Trm cells on day 3 and 8 post infection revealed complete Th17-lineage dominance (no Th1, Tfh or Foxp3+ Tregs) with extensive functional plasticity involving cytotoxicity (ThCTL) as well as regulatory functions. Unexpectedly, the same clonotype hosted cells with different Th17 subcluster functions (IL-17, IL-22), Tr1 cells and ThCTLs, suggesting a tissue and context-dependent differentiation of reactivated Th17 Trm cells. A gene set enrichment analysis demonstrated up- regulation of regulatory genes in the day 8 recovery phase. Contrary to present thinking lung M2e- specific Th17 Trm cells are sufficient for controlling infection and for preventing tissue injury. These findings will have strong implications for vaccine development.

ORGANISM(S): Mus musculus

PROVIDER: GSE161938 | GEO | 2022/06/29

REPOSITORIES: GEO

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