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


CONCLUSIONS
Cross-talk between T cells and HNEC results in activation of the latter and increases their contribution to airway inflammation and virus clearance.
Division of Pulmonary Medicine, Geneva University Hospitals, Geneva, Switzerland. Lan.H.Jornot@hcuge.ch
Lan
L
Jornot
Samuel
S
Cordey
Assunta
A
Caruso
Christine
C
Gerber
Marija
M
Vukicevic
Caroline
C
Tapparel
Laurent
L
Kaiser
Danielle
D
Burger
Eddy
E
Roosnek
Jean Silvain
JS
Lacroix
Thierry
T
Rochat
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009666:Nose / Q000473:pathology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D012229:Rhinovirus / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D012995:Solubility / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054357:Chemokine CXCL10; D015850:Interleukin-6; D016209:Interleukin-8; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II