IL-4 increases type 2, but not type 1, cytokine production in CD8+ T cells from mild atopic asthmatics.
BACKGROUND
Virus infections are the major cause of asthma exacerbations. CD8+ T cells have an important role in antiviral immune responses and animal studies suggest a role for CD8+ T cells in the pathogenesis of virus-induced asthma exacerbations. We have previously shown that the presence of IL-4 during stimulation increases the frequency of IL-5-positive cells and CD30 surface staining in CD8+ T cells from healthy, normal subjects. In this study, we investigated whether excess IL-4 during repeated TCR/CD3 stimulation of CD8+ T cells from atopic asthmatic subjects alters the balance of type 1/type 2 cytokine production in favour of the latter.


METHODS
Peripheral blood CD8+ T cells from mild atopic asthmatic subjects were stimulated in vitro with anti-CD3 and IL-2 +/- excess IL-4 and the expression of activation and adhesion molecules and type 1 and type 2 cytokine production were assessed.


RESULTS
Surface expression of very late antigen-4 [VLA-4] and LFA-1 was decreased and the production of the type 2 cytokines IL-5 and IL-13 was augmented by the presence of IL-4 during stimulation of CD8+ T cells from mild atopic asthmatics.


CONCLUSIONS
These data suggest that during a respiratory virus infection activated CD8+ T cells from asthmatic subjects may produce excess type 2 cytokines and may contribute to asthma exacerbation by augmenting allergic inflammation.
Department of Respiratory Medicine, National Heart and Lung Institute, Wright Fleming Institute for Infection and Immunity, Imperial College London, Norfolk Place, London, UK. l.stanciu@imperial.ac.uk
Luminita A
LA
Stanciu
Kevan
K
Roberts
Nikolaos G
NG
Papadopoulos
Sang-Heon
SH
Cho
Stephen T
ST
Holgate
Anthony J
AJ
Coyle
Sebastian L
SL
Johnston
D000328:Adult; D001249:Asthma / Q000145:classification / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1 / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D039041:Integrin alpha4beta1; D018793:Interleukin-13; D015848:Interleukin-5; D016169:Lymphocyte Function-Associated Antigen-1; D015847:Interleukin-4