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

Influenza Other Respir Viruses. 2016 Sep;10(5):438-42. doi: 10.1111/irv.12394. Epub 2016 May 17.

Abstract

Influenza viruses are a continuous threat to humans because of their ability to cross species barriers and adapt to new hosts. 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. Additionally, the fact that many CTLs recognize epitopes shared between different influenza strains offers the potential for broad cross-strain immunity. 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. We developed a novel CTL assay that utilizes fully differentiated nasal human epithelial 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. Modeling of the natural interaction process between the primary cell type that supports the productive replication of influenza and immune cells may allow us to put in perspective CTLs as a correlate of immunity to influenza in humans.

Keywords: Cytotoxic T lymphocytes; influenza virus; lysis; nasal human epithelial cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, American Recovery and Reinvestment Act

MeSH terms

  • Animals
  • Coculture Techniques
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • Dogs
  • Epithelial Cells / virology*
  • Epitopes
  • Host-Pathogen Interactions*
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H1N1 Subtype / physiology
  • Influenza A Virus, H3N8 Subtype / immunology*
  • Influenza A Virus, H3N8 Subtype / physiology
  • Madin Darby Canine Kidney Cells
  • Nasal Mucosa / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Virus Replication

Substances

  • Epitopes