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IFN-γ but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis

Authors


L. W. Poulter, Department of Clinical Immunology, Royal Free and University College School of Medicine, Rowland Hill Street, London NW3 2PF, UK. E-mail: lenpee@rfhsm.ac.uk

Abstract

Background Previous observations have established that IFN-γ 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-γ 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-γ+ 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-γ+ (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.

Conclusion The evidence supports the hypothesis that Th1/Th2 imbalance in asthmatic inflammation may be a result of premature apoptosis within the Th1 subset.

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