Memory cytotoxic SARS-CoV-2 spike protein-specific CD4+ T cells associate with viral control

Little is known of the role of cytotoxic CD4+ T-cells in the control of viral replication. Here, we investigate CD4+ T-cell responses to three dominant SARS-CoV-2 epitopes and evaluate antiviral activity, including cytotoxicity and antiviral cytokine production. Diverse T cell receptor (TCR) usage including public TCRs were identified; surprisingly, cytotoxic CD4+ T-cells were found to have signalling and cytotoxic pathways distinct from classical CD8+ T-cells, with increased expression of chemokines and tissue homing receptors promoting migration. We show the presence of cytolytic CD4+ T-cells during primary infection associates with COVID-19 disease severity. Robust immune memory 6-9 months post-infection or vaccination provides CD4+ T-cells with potent antiviral activity. Our data support a model where CD4+ killer cells drive immunopathogenesis during primary infection and CD4+ memory responses are protective during secondary infection. Our study highlights the unique features of cytotoxic CD4+ T-cells that use distinct functional pathways, providing preventative and therapeutic opportunities.

• Publication year

  2022

• Venue

  Unknown venue

• Publication date

  2022-02-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.21203/rs.3.rs-1317569/v1
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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