Increased Airway T Regulatory Cells in Asthmatic Subjects

Abstract

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. 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. 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(+). 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. 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.