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

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

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  • 1Division of Immunology, Children's Hospital Boston, Boston, MA 02115, USA.



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.


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.


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.


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.

Copyright 2006 Massachusetts Medical Society.

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