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Mucosal Immunol . Lung influenza virus specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung a

tetano

Editor, Senior Moderator
Mucosal Immunol


. 2024 Jun 6:S1933-0219(24)00050-3.
doi: 10.1016/j.mucimm.2024.06.001. Online ahead of print. 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[SUP] 1 [/SUP], Julie C Worrell[SUP] 1 [/SUP], Chiara Pirillo[SUP] 2 [/SUP], Euan Brennan[SUP] 1 [/SUP], Andreu Masdefiol Garriga[SUP] 3 [/SUP], Joshua I Gray[SUP] 1 [/SUP], Thomas Purnell[SUP] 1 [/SUP], Edward W Roberts[SUP] 2 [/SUP], Megan Kl MacLeod[SUP] 4 [/SUP]



Affiliations
Free article 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, characterising 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 MHCII+ 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 at lung airways but reduced interferon-γ expression by IAV-specific immunodominant memory CD4 T cells. The immunodominant CD4 T cells expressed higher levels of 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 antibody. These data suggest that sustained antigen presentation in the lung impacts on the formation of memory CD4 T cells by regulating their cytokine production and location.

Keywords: PD1; antigen presentation; influenza A virus; lung; memory CD4 T cell.

 
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