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

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Hargrave, Kerrie E. and Worrell, Julie C. and Pirillo, Chiara and Brennan, Euan and Masdefiol Garriga, Andreu and Gray, Joshua I. and Purnell, Thomas and Roberts, Edward W. and MacLeod, Megan K.L. (2024) Lung influenza virus-specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells. Mucosal Immunology, 17 (5). pp. 843-857. ISSN 1933-0219 (https://doi.org/10.1016/j.mucimm.2024.06.001)

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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.

ORCID iDs

Hargrave, Kerrie E. ORCID logoORCID: https://orcid.org/0000-0001-6015-4616, Worrell, Julie C., Pirillo, Chiara, Brennan, Euan, Masdefiol Garriga, Andreu, Gray, Joshua I., Purnell, Thomas, Roberts, Edward W. and MacLeod, Megan K.L.;
CORE (COnnecting REpositories)