Expression of surface markers on peripheral CD4<+>CD25<high> T cells in patients with atopic asthma: role of inhaled corticosteroid
Background CD4<+>CD25<+> regulatory T cells (Tregs) mediate immune suppression through cell-cell contact with surface molecules, particularly cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), and transforming growth factor β (TGF-β), but little is known about the exact role of Tregs in the pathogenesis of asthma. This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells derived Tregs in patients with atopic asthma and healthy subjects, and to investigate the role of inhaled corticosteroid on them. Methods Expression of surface molecules on CD4<+>CD25 <high> Tregs was detected by flow cytometry. The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro. Total serum immunoglobulin E (IgE) and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay, respectively. Results Equivalent numbers of peripheral Tregs were found in patients with atopic asthma (stable and acute) and healthy subjects. Tregs preferentially expressed CTLA-4, GITR, toll-like receptor 4 (TLR4), latency-associated peptide (LAP/TGF-β1), and forkhead box P3 (FOXP3). Patients with acute asthma had decreased numbers of CD4<+>CD25<high>LAP<+> T cells relative to healthy subjects and stable asthmatics. Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently. Furthermore, the percentages of Tregs expressing LAP negatively correlated with total serum IgE levels and severity of asthma, while positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma. Conclusions Our data suggest that membrane-bound TGF-β1 is a potential candidate for predicting the severity of asthma, and may contribute to the sustained remission of asthma. Strategies targeting Treg cells on their surface markers, especially TGF-β1, are promising for future therapy of asthma.
asthma atopy glucocorticoids regulatory T cells TGF-β
ZHANG Qian YIN Kai-sheng QIAN Fen-hong LIU Hua ZHOU Lin-fu HUANG Mao ZHANG Xi-long
Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
国际会议
上海
英文
278-288
2007-11-03（万方平台首次上网日期，不代表论文的发表时间）