Virus-induced eosinophil mediator release requires antigen-presenting and CD4+ T cells.
BACKGROUND
The most frequent trigger of asthma exacerbation is infection with common airway viruses; however, the precise mechanism regulating such severe reactions is not understood. The presence of airway eosinophil products is a unique feature detected in asthmatic airways. Using an animal model, we previously demonstrated that T cells play an important role in regulating an eosinophil-dependant pathway of virus-induced airway hyperreactivity. We hypothesize that human eosinophils respond to viruses, although only after interaction with T cells.


OBJECTIVE
We sought to determine whether eosinophils can respond to airway viruses in vitro and determine the mechanism of response.


METHODS
An in vitro coculture model of human eosinophils, antigen-presenting cells, and T cells was used with parainfluenza virus, respiratory syncytial virus, or rhinovirus. We measured release of eosinophil peroxidase (EPO) in concert with T-cell proliferation, cytokine release, and changes in T-cell phenotype.


RESULTS
The viruses induced release of EPO when coincubated in the presence of antigen-presenting cells (dendritic cells or macrophages) and T cells. Virus-mediated release was associated with proliferation of CD3(+)CD4(+) T cells and release of cytokines. UV inactivation of the virus did not prevent virus-induced EPO release or T-cell proliferation. Proliferating CD4(+) T cells show increased expression of CD25 and CD45RO. CD8(+) T cells were not activated.


CONCLUSIONS
Virus-induced EPO release can occur in the context of antigen presentation to CD4(+) T cells.
Davoine
Francis
F
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Cao
Min
M
Wu
Yingqi
Y
Ajamian
Farnam
F
Ilarraza
Ramses
R
Kokaji
Andy I
AI
Moqbel
Redwan
R
Adamko
Darryl J
DJ
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D047209:Eosinophil Peroxidase / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D012229:Rhinovirus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes; D014780:Viruses / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D047209:Eosinophil Peroxidase