Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics.
We recently demonstrated bronchial mucosal expression of IL-4 and IL-5 at the mRNA and protein level in both atopic and nonatopic (intrinsic) asthma. In this report, using double immunohistochemistry (IHC) and in situ hybridization (ISH), we show that 70% of IL-4 and IL-5 mRNA+ signals co-localized to CD3+ T cells, the majority (>70%) of which were CD4+, although CD8+ cells also expressed IL-4 and IL-5 mRNA. The remaining IL-4 and IL-5 mRNA signals co-localized to mast cells and eosinophils. The cellular distribution of these mRNA species did not differ between atopic and nonatopic asthmatics. In contrast, double IHC showed that IL-4 and IL-5 immunoreactivity was predominantly associated with eosinophils and mast cells, with few IL-5 or IL-4 immunoreactive CD3+ T cells detectable. However, total IL-4- or IL-5-positive cells detected by IHC were <40% of the total mRNA+ cells, raising the possibility that insufficient cytokine protein accumulated within T cells to enable detection by IHC. We conclude that: 1) in atopic and nonatopic asthma CD8+ T cells, in addition to CD4+ T cells, mast cells and eosinophils express mRNA for IL-4 and IL-5; 2) whereas IL-4 and IL-5 mRNA expression was associated mainly with T cells, immunoreactivity for the corresponding protein products was detectable predominantly in eosinophils and mast cells; and 3) this discrepancy may be partly attributable to the relative insensitivity of double IHC technique that does not allow detection of cytokine protein in T cells where, unlike eosinophils and mast cells, there is no facility for storage and concentration in granules.
Ying
S
S
Allergy and Clinical Immunology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
Humbert
M
M
Barkans
J
J
Corrigan
C J
CJ
Pfister
R
R
Menz
G
G
Larché
M
M
Robinson
D S
DS
Durham
S R
SR
Kay
A B
AB
D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis
D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4