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

Respirology. 2015 May;20(4):579-86. doi: 10.1111/resp.12497. Epub 2015 Feb 25.

Abstract

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.

Keywords: Escherichia coli lipopolysaccharide; bronchoalveolar lavage fluid; pulmonary inflammation; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchoalveolar Lavage Fluid / cytology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • Endotoxins
  • Flow Cytometry
  • Humans
  • Lipopolysaccharides / poisoning
  • Lymphocyte Count
  • Male
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Respiratory Distress Syndrome / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Young Adult

Substances

  • Endotoxins
  • Lipopolysaccharides