title: Rhinovirus has the unique ability to directly activate human T cells in vitro.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors: Ramses
authors: R
authors: Ilarraza
authors: Yingqi
authors: Y
authors: Wu
authors: Christopher D
authors: CD
authors: Skappak
authors: Farnam
authors: F
authors: Ajamian
authors: David
authors: D
authors: Proud
authors: Darryl J
authors: DJ
authors: Adamko
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016923:Cell Death / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000821:virology; D005802:Genes, MHC Class II / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000821:virology; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology; D015289:Leukotrienes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D010850:Picornaviridae Infections / Q000276:immunology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000821:virology; D012229:Rhinovirus / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D016207:Cytokines; D015289:Leukotrienes; D016328:NF-kappa B; D051193:Toll-Like Receptors; D048031:JNK Mitogen-Activated Protein Kinases