CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma

N Engl J Med. 2006 Mar 16;354(11):1117-29. doi: 10.1056/NEJMoa053614.


Background: Bronchial asthma is associated with an inflammatory process that is characterized by the presence in the airways of large numbers of CD4+ T cells producing interleukin-4 and interleukin-13. However, the CD4 antigen is expressed not only by class II major histocompatibility complex (MHC)-restricted CD4+ T cells, but also by a newly identified subgroup of T cells, CD1d-restricted natural killer T cells. These cells express a conserved (invariant) T-cell receptor and have a potent immunoregulatory function. Because mouse models of allergic asthma indicate that natural killer T cells are required for the development of allergen-induced airway hyperreactivity, we hypothesized that natural killer T cells play an important role in human asthma.

Methods: We used CD1d-tetramers, antibodies specific for natural killer T cells, as well as reverse-transcriptase-polymerase-chain-reaction analysis of the invariant T-cell receptor of natural killer T cells to assess the frequency and distribution of natural killer T cells in the lungs and in the circulating blood of 14 patients with asthma.

Results: About 60 percent of the pulmonary CD4+CD3+ cells in patients with moderate-to-severe persistent asthma were not class II MHC-restricted CD4+ T cells but, rather, natural killer T cells. The natural killer T cells expressed an invariant T-cell receptor and produced type 2 helper cytokines. In contrast, the CD4+ T cells found in the lungs of patients with sarcoidosis were conventional CD4+CD3+ T cells, not natural killer T cells.

Conclusions: Together with studies in mice indicating a requirement for natural killer T cells in the development of allergen-induced airway hyperreactivity, our results strongly suggest that CD4+ natural killer T cells play a prominent pathogenic role in human asthma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD1
  • Asthma / immunology*
  • Bronchoalveolar Lavage Fluid / immunology*
  • CD3 Complex
  • CD4-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-13 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Killer Cells, Natural* / immunology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Reference Values
  • Sarcoidosis / immunology
  • T-Lymphocytes / immunology*


  • Antigens, CD1
  • CD3 Complex
  • Interleukin-13
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Interleukin-4
  • Interferon-gamma