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

• Published in: PloS one 2011-10, Vol.6 (10), p.e26293
• Main Authors: Jornot, Lan, Cordey, Samuel, Caruso, Assunta, Gerber, Christine, Vukicevic, Marija, Tapparel, Caroline, Kaiser, Laurent, Burger, Danielle, Roosnek, Eddy, Lacroix, Jean Silvain, Rochat, Thierry
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Antiviral agents; Asthma; Biology; CD28 antigen; CD3 antigen; Cell activation; Cell Differentiation - drug effects; Cell Differentiation - immunology; Chemokine CXCL10 - genetics; Chemokine CXCL10 - metabolism; Clone Cells; Cloning; Collagen; Consent; CXCL10 protein; Cytokines; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelial Cells - virology; Ethics; Gene expression; Gene Expression Regulation - drug effects; Hematology; Hospitals; Human subjects; Humans; Infections; Infectious diseases; Inflammation; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Interleukin 6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Interleukin-8 - genetics; Interleukin-8 - metabolism; Kinases; Laboratories; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocyte Count; Lymphocytes; Lymphocytes T; Medicine; Messenger RNA; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nose - pathology; Penicillin; Proteins; Receptors, Tumor Necrosis Factor, Type II - metabolism; Respiratory tract; Respiratory tract diseases; Review boards; Rhinovirus; Rhinovirus - drug effects; Rhinovirus - immunology; Rhinovirus - physiology; Smooth muscle; Solubility - drug effects; T cells; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Virology; Virus Replication - drug effects; Viruses; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0026293

T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV). 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. 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. Cross-talk between T cells and HNEC results in activation of the latter and increases their contribution to airway inflammation and virus clearance.