PMID- 18298910 OWN - NLM STAT- MEDLINE DCOM- 20080403 LR - 20111117 IS - 0366-6999 (Print) IS - 0366-6999 (Linking) VI - 121 IP - 3 DP - 2008 Feb 5 TI - Expression of surface markers on peripheral CD4+CD25high T cells in patients with atopic asthma: role of inhaled corticosteroid. PG - 205-12 AB - 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 beta (TGF-beta), 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 effect of inhaled corticosteroid on them. METHODS: The 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-beta1), and forkhead box P3 (FOXP3). Patients with acute asthma had decreased numbers of CD4(+)CD25(high)LAP(+) T cells compared 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 were negatively correlated with total serum IgE levels and severity of asthma, but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma. CONCLUSIONS: The results suggest that membrane-bound TGF-beta1 is a potential candidate for predicting the severity of asthma, and may contribute to the sustained remission of asthma. Strategies targeting Tregs on their surface markers, especially TGF-beta1, are promising for future therapy of asthma. FAU - Zhang, Qian AU - Zhang Q AD - Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China. FAU - Qian, Fen-hong AU - Qian FH FAU - Liu, Hua AU - Liu H FAU - Zhou, Lin-fu AU - Zhou LF FAU - Huang, Mao AU - Huang M FAU - Zhang, Xi-long AU - Zhang XL FAU - Yin, Kai-sheng AU - Yin KS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Chin Med J (Engl) JT - Chinese medical journal JID - 7513795 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation) RN - 0 (CTLA-4 Antigen) RN - 0 (CTLA4 protein, human) RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Glucocorticoid-Induced TNFR-Related Protein) RN - 0 (Receptors, Nerve Growth Factor) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (TLR4 protein, human) RN - 0 (TNFRSF18 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (Transforming Growth Factor beta1) RN - 51333-22-3 (Budesonide) SB - IM MH - Administration, Inhalation MH - Adrenal Cortex Hormones/*administration & dosage MH - Adult MH - Antigens, CD/blood MH - Antigens, Differentiation/blood MH - Asthma/drug therapy/*immunology MH - Budesonide/pharmacology MH - CTLA-4 Antigen MH - Female MH - Forkhead Transcription Factors/blood MH - Glucocorticoid-Induced TNFR-Related Protein MH - Humans MH - Male MH - Middle Aged MH - Receptors, Nerve Growth Factor/blood MH - Receptors, Tumor Necrosis Factor/blood MH - T-Lymphocytes, Regulatory/drug effects/*immunology MH - Toll-Like Receptor 4/blood MH - Transforming Growth Factor beta1/blood EDAT- 2008/02/27 09:00 MHDA- 2008/04/04 09:00 CRDT- 2008/02/27 09:00 PHST- 2008/02/27 09:00 [pubmed] PHST- 2008/04/04 09:00 [medline] PHST- 2008/02/27 09:00 [entrez] PST - ppublish SO - Chin Med J (Engl). 2008 Feb 5;121(3):205-12.