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Background: T regulatory cells (Tregs) may play a role in the suppression of effector lymphocyte activity in asthma. We hypothesized that Treg numbers would be increased in patients with more severe asthma. We also investigated the regulatory function of CD4 cells by expression of cytotoxic T-lymphocyte antigen 4 (CTLA4), and the number of these cells that are intraepithelial lymphocytes expressing CD103., Objectives: The primary aim was to investigate Treg numbers in the BAL of patients with moderate to severe asthma compared with mild asthma and healthy controls. The secondary aim was to investigate BAL CD4(+)CTLA4 and CD4(+)CD103 expression in these groups., Methods: Airway lymphocytes obtained by bronchoscopy from healthy control subjects (six) and patients with mild (15) and moderate to severe (13) asthma were characterized by multiparameter flow cytometric analysis using three methods to determine the numbers of CD4(+) Treg cells: CD4(+)CD25(bright), CD4(+)CD25(+)CD127(-), and CD4(+)FoxP3(+)., Results: The %CD4(+)FoxP3(+) Tregs were increased in the BAL of patients with moderate to severe asthma (median 4.8%) compared with both mild asthma patients (median 2.5%, P = .03) and healthy subjects (median 0.95, P = .003). Similar findings were observed for CD4(+)CD25(+)CD127(-) Treg numbers, but not CD4CD25(bright). CD4(+) CTLA4 and CD103 expressions were raised in moderate to severe asthma patients compared with those with mild asthma and healthy controls., Conclusions: The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, is increased in moderate to severe asthma. CD4(+)CD103(+) intraepithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.

Background: The numbers of airway CD8 and B lymphocytes are increased in COPD patients, suggesting an autoimmune process. CD4-regulatory T cells control autoimmunity but have not been studied in patients with COPD., Objective: To compare T-regulatory cell numbers in the BAL from COPD patients, smokers with normal lung function, and healthy nonsmokers (HNS)., Methods: BAL and peripheral blood mononuclear cell (PBMC) samples were obtained from 26 COPD patients, 19 smokers, and 8 HNS. Flow cytometry was performed for regulatory phenotypic markers., Results: COPD patients had increased BAL CD8 numbers compared to smokers and HNS. CD4 numbers were similar between groups. There was increased BAL CD4CD25(bright) expression in smokers (median 28.8%) and COPD patients (median 23.1%) compared to HNS (median 0%). Increased FoxP3 expression was confirmed in BAL CD4CD25(bright) cells. BAL CD4CD25 cells expressed less CD27 compared to PBMCs, suggesting weaker functional regulatory ability., Clinical Implications: Chronic cigarette smoke exposure up-regulates airway CD4 regulatory cell numbers. Their function may be to control pulmonary inflammation.