Abstract
Lung-resident primary memory CD8+ Tcell populations (Trm) induced by a single influenza infection decline within months, rendering the host susceptible to new heterosubtypic influenza infections. Here, we demonstrate that, relative to single virus exposure, repeated antigen exposure dramatically alters the dynamics of influenza-specific lung Trm populations. Lung Trm derived from repeatedly stimulated circulating memory CD8+ Tcells exhibit extended durability and protective heterosubtypic immunity relative to primary lung Trm. Parabiosis studies reveal that the enhanced durability of lung Trm after multiple antigen encounters resulted from the generation of long-lasting circulating effector memory (Tem) populations, which maintained the ability to be recruited to the lung parenchyma and converted to Trm, in combination with enhanced survival of these cells in the lung. Thus, generating a long-lasting Trm precursor pool through repeated intranasal immunizations might be a promising strategy to establish long-lasting lung Trm-mediated heterosubtypic immunity against influenza.
Highlights
Based on health and socioeconomic impact, influenza virus infections are a major global health burden (Kondrich and Rosenthal, 2017; Nicholson et al, 2003)
Of note, based on published data indicating that 3°M cells proliferate less than naive CD8 T cells in response to systemic infection (Wirth et al, 2010) and in order to achieve similar frequencies of circulating 105 spleen-derived primary memory (1°M) and 4°M P14 cells, mice received 105 3°M P14 cells
The circulating precursor populations used for adoptive transfer lacked cells expressing both CD69 and CD103, which represent the canonical markers of lung Trm (Wakim et al, 2013; Wu et al, 2014)
Summary
Based on health and socioeconomic impact, influenza virus infections are a major global health burden (Kondrich and Rosenthal, 2017; Nicholson et al, 2003). Reassortment of the segmented influenza virus genome in animal reservoirs can result in new HA sequences (antigenic shift) (Kim et al, 2018) that have not previously circulated in humans and have the potential for pandemic infections (Kim et al, 2018) It has been well documented in humans and rodent models that influenza-specific CD8+ T cells targeting conserved internal proteins of the virus can control virus titers and limit disease development in the absence of neutralizing antibodies (Altenburg et al, 2015; Kreijtz et al, 2007; McMichael et al, 1983; Sridhar et al, 2013). Inducing a potent and long-lasting influenza-specific Trm population should be considered as a potentially useful vaccination target
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
