An increased alveolar CD4+CD25+Foxp3+T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality

Cell therapy may become an option for lung injury treatment. However, no data are available on the alveolar presence and time course of CD4+ CD25 + Foxp3 + T-regulatory lymphocyte cells (Tregs) in acute respiratory distress syndrome (ARDS). Accordingly, we (1) measured the ratio of CD4 + CD25 + Foxp3 + Tregs to all (CD4+) lymphocytes in the bronchoalveolar lavage (BAL) of ARDS patients and of control subjects without lung disease and (2) assessed their impact on 30-day mortality. In a prospective study, the ratios of CD4 + CD25 + Foxp3 + T-regulatory cells to all CD4+ cells were measured (FACS) within 24 h of the patients' ICU referral in the BAL and in the blood of 47 patients with ARDS (32 males, 15 females; mean age 44 years +/- 13) as well as in 8 controls undergoing elective abdominal surgery (5 men, 3 women; mean age 49 years +/- 4). BAL concentrations of several cytokines were also measured in ARDS patients. Tregs were detected in the BAL of control subjects and ARDS patients. However, the mean ratio of Tregs to all CD4+ lymphocytes was threefold greater in ARDS non-survivors (16.5 %; p = 0.025) and almost twofold greater in ARDS survivors (9.0 %; p = 0.015) compared to controls (5.9 %). Multivariate Cox regression analysis revealed the ratio of CD4 + CD25 + Foxp3 + T-regulatory lymphocytes to all CD4+ lymphocytes in the BAL to be an important and independent prognostic factor for 30-day survival (HR 6.5; 95 % CI, 1.7-25; p = 0.006). An increased T-regulatory cell ratio in the admission BAL of patients with ARDS is an important and independent risk factor for 30-day mortality.