IL-4 differentiates naive CD8+ T cells to a "Th2-like" phenotype: a link between viral infections and bronchial asthma.
Viral infections of the lung have been postulated to be a major factor in the etiology of bronchial asthma, a disease characterized by eosinophilic inflammation of the airways. In addition, upper respiratory tract infection in asthmatic individuals results in an exacerbation of the disease. Nevertheless, the mechanisms by which viral infection leads to disease exacerbation are poorly understood. CD8+ T cells play an important role in the host defense responses against viral infection, although to date, there are no reports to suggest that CD8+ T cells play any role in eosinophil recruitment. In the present study, we report that CD8+ T cells activated by either immobilized CD3 mAb or specific antigen can switch to a phenotype that produces Th2 cytokines and secretes less IFN-gamma. Moreover, in vivo, if a lung mucosal Th2 immune response exists, then antigen-specific activation of CD8 cells results in the development of lung eosinophilic inflammation mediated by the secretion of IL-5 from CD8+ T cells. These results may explain the link between viral infections and bronchial asthma, as this IL-4-dependent switch to CD8+ T cells to IL-5 secretion may not only exacerbate asthma by recruiting eosinophils into the lungs, but the impaired IFN-gamma production may also lead to delayed viral clearance.
Department of Asthma and Allergy, CIBA GEIGY AG, Basel, Switzerland.
A J
AJ
Coyle
C
C
Bertrand
S
S
Tsuyuki
H
H
Pircher
S
S
Walti
G
G
Le Gros
F
F
Erard
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D012141:Respiratory Tract Infections / Q000150:complications*; D018418:Th2 Cells / Q000378:metabolism*; D014764:Viral Proteins / Q000494:pharmacology; D014777:Virus Diseases / Q000150:complications* / Q000378:metabolism
D014764:Viral Proteins; D015847:Interleukin-4