Scientific Publications by FDA Staff

Influenza Other Respir Viruses 2016 Sep;10(5):438-42

In vitro modeling of the interaction between human epithelial cells and lymphocytes upon influenza infection.

Ilyushina NA, Wright PF

Influenza viruses are a continuous threat to humans because of their ability to cross species barriers and adapt to new hosts. It has been estimated that 5-15% of the world population are infected during annual outbreaks and that these infections result in one million deaths every year.1 Influenza virions infect the cells of respiratory pseudostratified columnar epithelium consisting of a single layer of three major cells types, namely ciliated, goblet and Clara cells.2 Data from murine studies, along with limited human data, suggest that CD8+ cytotoxic T lymphocytes (CTL) that recognize conserved epitopes of structural influenza proteins are the main mediators of influenza virus clearance.3-7 Additionally, the fact that many CTLs recognize epitopes shared between different influenza strains offers the potential for broad cross-strain immunity.8-10 However, the mechanisms of cellular immunity against influenza viruses are poorly defined in humans, where the CTL response has been hard to measure and interpret.4,8,9,11 In the present study we developed a novel CTL assay that utilizes fully differentiated nasal human epithelial (NHE) cells taken from volunteers as permissive targets for autologous peripheral blood-derived influenza virus-specific cytotoxic T lymphocytes. This in vitro system of human lymphocyte-epithelial cell co-cultures can be considered as the closest approximation to events in vivo and can be employed for studying the interactions between the pathogen and human host.