T cell subsets in human airways prior to and following endobronchial administration of endotoxin

TY - JOUR

T1 - T cell subsets in human airways prior to and following endobronchial administration of endotoxin

AU - Ronit, Andreas

AU - Plovsing, Ronni R

AU - Gaardbo, Julie C

AU - Berg, Ronan M G

AU - Hartling, Hans J

AU - Konge, Lars

AU - Iversen, Martin

AU - Ullum, Henrik

AU - Møller, Kirsten

AU - Nielsen, Susanne Dam

N1 - © 2015 Asian Pacific Society of Respirology.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Background and objectives Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought to determine whether pro- and anti-inflammatory T cells are involved in the local immune response to lung inflammation. Methods Bronchoalveolar lavage (BAL) was performed in 15 healthy volunteers, after which Escherichia coli LPS (4 ng/kg) was administered. BAL was repeated at 2, 4, 6, 8 or 24 h after instillation of LPS. Results BALF CD4+ and CD8+ T cells were characterized by expression of activation markers (HLA-DR+CD38+), the proportion of cells expressing naïve markers (CD45RA+CD27+CCR7+) was lower, and that of cells expressing effector memory markers (CD45RA-CD27+CCR7-) was higher, compared with peripheral blood. Bronchial LPS induced a local inflammatory response with recruitment of CD4+ (P = 0.014), CD8+ T cells (P = 0.034), an increase in the proportion of CD4+CD25+CD127lowFoxp3+ regulatory T cells (Tregs) (P = 0.045) and a tendency towards an increase in CD4+CD161+ cells (P = 0.071) were observed. Conclusions A unique distribution of T cells with little day-to-day variation was found in human airways. An increase in Tregs after endobronchial LPS suggests a role for Tregs during early stages of pulmonary inflammation. In this human experimental study using bronchial instillation of endotoxin (LPS) the kinetics of specific T-cell subsets were studied. Increased frequency of Tregs was observed, thus suggesting that these cells may aid in the resolution of acute lung inflammation.

AB - Background and objectives Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought to determine whether pro- and anti-inflammatory T cells are involved in the local immune response to lung inflammation. Methods Bronchoalveolar lavage (BAL) was performed in 15 healthy volunteers, after which Escherichia coli LPS (4 ng/kg) was administered. BAL was repeated at 2, 4, 6, 8 or 24 h after instillation of LPS. Results BALF CD4+ and CD8+ T cells were characterized by expression of activation markers (HLA-DR+CD38+), the proportion of cells expressing naïve markers (CD45RA+CD27+CCR7+) was lower, and that of cells expressing effector memory markers (CD45RA-CD27+CCR7-) was higher, compared with peripheral blood. Bronchial LPS induced a local inflammatory response with recruitment of CD4+ (P = 0.014), CD8+ T cells (P = 0.034), an increase in the proportion of CD4+CD25+CD127lowFoxp3+ regulatory T cells (Tregs) (P = 0.045) and a tendency towards an increase in CD4+CD161+ cells (P = 0.071) were observed. Conclusions A unique distribution of T cells with little day-to-day variation was found in human airways. An increase in Tregs after endobronchial LPS suggests a role for Tregs during early stages of pulmonary inflammation. In this human experimental study using bronchial instillation of endotoxin (LPS) the kinetics of specific T-cell subsets were studied. Increased frequency of Tregs was observed, thus suggesting that these cells may aid in the resolution of acute lung inflammation.

U2 - 10.1111/resp.12497

DO - 10.1111/resp.12497

M3 - Journal article

C2 - 25711164

SN - 1323-7799

VL - 20

SP - 579

EP - 586

JO - Respirology

JF - Respirology

IS - 4

ER -