Rhinovirus has the unique ability to directly activate human T cells in vitro - 30/01/13
Corresponding author: Darryl J. Adamko, MD, FRCP(C), Department of Pediatrics, 270 Ellis Hall, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8, Canada.Abstract |
Background |
Rhinovirus infection is a leading cause of exacerbation of airway diseases. We hypothesize that airway viruses activate inflammatory cells, inducing airway dysfunction. We have previously shown that airway viruses can induce eosinophil degranulation when cocultured with T cells and monocyte-derived dendritic cells (moDCs). These findings suggested that antigen presentation was important for T-cell activation.
Objective |
Given the clinical importance of rhinovirus, we sought to determine whether it had any unique abilities to activate inflammatory cells compared with another common virus, such as respiratory syncytial virus (RSV).
Methods |
We cocultured combinations of human leukocytes (T cells, moDCs, and eosinophils) with each virus. Using assays of BrdU incorporation, flow cytometry, and ELISA, we measured T-cell activation, rhinovirus expression, T-cell death, and eosinophil cysteinyl leukotriene release.
Results |
In contrast to RSV, rhinovirus induced T-cell activation without the involvement of moDCs. Without moDCs, rhinovirus induced T-cell proliferation of both CD4 and CD8+ cells, cytokine production, and ultimately, eosinophil stimulation. Although chloroquine inhibited RSV-induced activation of T cells through moDCs, rhinovirus was not inhibited; UV inactivation did block the rhinovirus effect. We also found that T cells could be infected by rhinovirus in vitro and within human nasal explant tissue. Although Toll-like receptors did not appear to be involved in T-cell activation, antagonists of Jun N-terminal kinase and nuclear factor κB did inhibit T-cell responses to rhinovirus.
Conclusion |
Rhinovirus has the unique ability to bypass antigen presentation and directly infect and activate human T cells. This could explain the strong association of rhinovirus with exacerbation of airway diseases.
Le texte complet de cet article est disponible en PDF.Key words : Asthma exacerbation, T cells, viral infection, rhinovirus, respiratory syncytial virus
Abbreviations used : APC, BrdU, CysLT, IKKε, ICAM-1, Jnk, MAP, MDA-5, MHC-I, MHC-II, moDC, NF-κB, poly(I:C), PRR, qPCR, RIG-I, RSV, RSV-UV, RV-UV, ssRNA, TBK, TCID50, TLR
Plan
| Supported by the Canadian Institutes of Health Research. D.J.A. was an Alberta Heritage Clinical Investigator. R.I. received funding from CONACyT-Mexico. D.P. holds a Canada Research Chair in Inflammatory Airway Diseases. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 395-404 - février 2013 Retour au numéro
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