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Previous Volume 354:1117-1129 March 16, 2006 Number 11 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Kay, A. B. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

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.

Source Information

From the Division of Immunology, Children's Hospital Boston, and the Department of Pediatrics, Harvard Medical School — both in Boston (O.A., R.H.D., D.T.U.); the Division of Pulmonary and Critical Care, Department of Medicine (J.L.F.), the Department of Pediatrics (E.G.H., D.T.U.), and the Department of Pathology (G.J.B.), Stanford University, Stanford, Calif.; the Division of Respiratory Medicine and Department of Medicine, Karolinska Institute, Stockholm (J.W.); and the Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, Calif. (M.K.).

Drs. Akbari and Faul contributed equally to this article.

Address reprint requests to Dr. Umetsu at the Division of Immunology, Children's Hospital Boston, Harvard Medical School, Karp Research Laboratories, 1 Blackfan Cir., Rm. 10127, Boston, MA 02115, or at dale.umetsu{at}childrens.harvard.edu.

Full Text of this Article

Related Letters:

Invariant Natural Killer T Cells in Bronchial Asthma
Thomas S. Y., Lilly C. M., Luster A. D., Pham-Thi N., de Blic J., Leite-de-Moraes M. C., Akbari O., Faul J. L., Umetsu D. T.
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N Engl J Med 2006; 354:2613-2616, Jun 15, 2006. Correspondence

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