Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease

N Engl J Med. 2007 Apr 5;356(14):1410-22. doi: 10.1056/NEJMoa064691.

Abstract

Background: The number of type 2 helper CD4+ T cells is increased in the airways of persons with asthma. Whether the majority of these cells are class II major-histocompatibility-complex-restricted cells or are among the recently identified CD1d-restricted invariant natural killer T cells is a matter of controversy. We studied the frequency of invariant natural killer T cells in the airways of subjects with mild or moderately severe asthma to investigate the possibility of an association between the number of invariant natural killer T cells in the airway and disease severity. We also studied whether an increased number of these cells is a feature of chronic obstructive pulmonary disease (COPD).

Methods: We enumerated invariant natural killer T cells by flow cytometry with the use of CD1d tetramers loaded with alpha-galactosylceramide and antibodies specific to the invariant natural killer T-cell receptor in samples of bronchoalveolar-lavage fluid, induced sputum, and bronchial-biopsy specimens obtained from subjects with mild or moderately severe asthma, subjects with COPD, and healthy control subjects. Real-time polymerase-chain-reaction analysis was performed on bronchoalveolar-lavage cells for evidence of gene expression of the invariant natural killer T-cell receptor.

Results: Fewer than 2% of the T cells obtained from all subjects on airway biopsy, bronchoalveolar lavage, and sputum induction were invariant natural killer T cells, with no significant differences among the three groups of subjects. No expression of messenger RNA for the invariant natural killer T-cell-receptor domains Valpha24 and Vbeta11 was detected in bronchoalveolar-lavage cells from subjects with asthma.

Conclusions: Invariant natural killer T cells are found in low numbers in the airways of subjects with asthma, subjects with COPD, and controls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / immunology*
  • Bronchi / immunology*
  • Bronchoalveolar Lavage Fluid / immunology*
  • CD3 Complex
  • Case-Control Studies
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Killer Cells, Natural* / immunology
  • Lymphocyte Count
  • Polymerase Chain Reaction
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • Sputum / immunology*
  • T-Lymphocytes* / immunology
  • Th2 Cells

Substances

  • CD3 Complex
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, IgG