T lymphocytes promote the antiviral and inflammatory responses of airway epithelial cells

PLoS One. 2011;6(10):e26293. doi: 10.1371/journal.pone.0026293. Epub 2011 Oct 14.


Hypothesis: T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV).

Methods: Differentiated primary human nasal epithelial cells (HNEC) grown on collagen-coated filters were exposed apically to HRV14 for 6 h, washed thoroughly and co-cultured with anti-CD3/CD28 activated T cells added in the basolateral compartment for 40 h.

Results: HRV14 did not induce IFNγ, NOS2, CXCL8 and IL-6 in HNEC, but enhanced expression of the T cell attractant CXCL10. On the other hand, HNEC co-cultured with activated T cells produced CXCL10 at a level several orders of magnitude higher than that induced by HRV14. Albeit to a much lower degree, activated T cells also induced CXCL8, IL-6 and NOS2. Anti-IFNγ antibodies and TNF soluble receptor completely blocked CXCL10 upregulation. Furthermore, a significant correlation was observed between epithelial CXCL10 mRNA expression and the amounts of IFNγ and TNF secreted by T cells. Likewise, increasing numbers of T cells to a constant number of HNEC in co-cultures resulted in increasing epithelial CXCL10 production, attaining a plateau at high IFNγ and TNF levels. Hence, HNEC activation by T cells is induced mainly by IFNγ and/or TNF. Activated T cells also markedly inhibited viral replication in HNEC, partially through activation of the nitric oxide pathway.

Conclusion: Cross-talk between T cells and HNEC results in activation of the latter and increases their contribution to airway inflammation and virus clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism
  • Clone Cells
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial Cells / virology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation
  • Interferon-gamma / metabolism
  • Interferon-gamma / pharmacology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Nose / pathology*
  • Receptors, Tumor Necrosis Factor, Type II / metabolism
  • Rhinovirus / drug effects
  • Rhinovirus / immunology*
  • Rhinovirus / physiology
  • Solubility / drug effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Virus Replication / drug effects


  • CXCL10 protein, human
  • CXCL8 protein, human
  • Chemokine CXCL10
  • Interleukin-6
  • Interleukin-8
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Interferon-gamma
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II