Lung influenza virus-specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells

Kerrie E. Hargrave, Julie C. Worrell, Chiara Pirillo, Euan Brennan, Andreu Masdefiol Garriga, Joshua I. Gray, Thomas Purnell, Edward W. Roberts, Megan K.L. MacLeod*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza A virus (IAV) infection leads to the formation of mucosal memory CD4 T cells that can protect the host. An in-depth understanding of the signals that shape memory cell development is required for more effective vaccine design. We have examined the formation of memory CD4 T cells in the lung following IAV infection of mice, characterizing changes to the lung landscape and immune cell composition. IAV-specific CD4 T cells were found throughout the lung at both primary and memory time points. These cells were found near lung airways and in close contact with a range of immune cells including macrophages, dendritic cells, and B cells. Interactions between lung IAV-specific CD4 T cells and major histocompatibility complex (MHC)II+ cells during the primary immune response were important in shaping the subsequent memory pool. Treatment with an anti-MHCII blocking antibody increased the proportion of memory CD4 T cells found in lung airways but reduced interferon-γ expression by IAV-specific immunodominant memory CD4 T cells. The immunodominant CD4 T cells expressed higher levels of programmed death ligand 1 (PD1) than other IAV-specific CD4 T cells and PD1+ memory CD4 T cells were located further away from MHCII+ cells than their PD1-low counterparts. This distinction in location was lost in mice treated with anti-MHCII antibodies. These data suggest that sustained antigen presentation in the lung impacts the formation of memory CD4 T cells by regulating their cytokine production and location.
Original languageEnglish
Pages (from-to)843-857
Number of pages15
JournalMucosal Immunology
Volume17
Issue number5
DOIs
Publication statusPublished - 9 Oct 2024

Keywords

  • influenza A virus
  • CD4 T cells
  • MHCII+ cells
  • lung influenza

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