IFN-gamma but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis.
BACKGROUND
Previous observations have established that IFN-gamma production is depressed in CD4+ T cells from atopic asthmatics compared with non-asthmatics.


OBJECTIVE
The aim of this study was to determine if decreased IFN-gamma production could be due to a dissociation between levels of apoptosis within the T cell subsets of the asthmatic bronchial wall.


METHODS
Twenty asthmatics (10 atopic and 10 non-atopic) and eight non-atopic non-asthmatics underwent bronchoscopy. Cryostat sections of these biopsies were investigated using immunohistological techniques to determine the relative number of CD4/FAS+ and CD4/Bcl-2+ cells. Detection of IFN-gamma+ and IL-4+ was combined with TUNEL staining to determine the proportions of the Th1 and Th2 cells undergoing apoptosis.


RESULTS
Experiments revealed raised proportions of activated CD4+ T cells as assessed by expression of HLA-DR and CD25+ expression in the asthmatic samples. Expression of Bcl-2 by the CD4+ cell population was significantly reduced in the asthmatic compared with the control group (P = 0.002). There was no significant difference in the expression of CD4+ Fas-ligand or the number of CD4+ undergoing apoptosis in the asthmatic and non-asthmatic groups. However, the IFN-gamma+ (P = 0.04) but not IL-4+ T cells in the asthmatic biopsies had significantly higher proportions of apoptotic cells compared with the control group.


CONCLUSIONS
The evidence supports the hypothesis that Th1/Th2 imbalance in asthmatic inflammation may be a result of premature apoptosis within the Th1 subset.
Cormican
L
L
Department of Respiratory Medicine, James Connolly Memorial Hospital, Dublin, Ireland.
O'Sullivan
S
S
Burke
C M
CM
Poulter
L W
LW
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001249:Asthma / Q000378:metabolism* / Q000473:pathology*; D001706:Biopsy; D001980:Bronchi / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D019254:Genes, bcl-2 / Q000235:genetics; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D015994:Incidence; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D006684:HLA-DR Antigens; D015847:Interleukin-4; D007371:Interferon-gamma