期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 131, 期 2, 页码 395-404出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.11.041
关键词
Asthma exacerbation; T cells; viral infection; rhinovirus; respiratory syncytial virus
资金
- Canadian Institutes of Health Research
- CONACyT-Mexico
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 kappa B 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. (J Allergy Clin Immunol 2013;131:395-404.)
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