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Activation of Nonclassical CD1d-Restricted NK T Cells Induces Airway Hyperreactivity in β₂-Microglobulin-Deficient Mice¹

Youngil I. Koh^2,*,, Hye Young Kim^2,*, Everett H. Meyer^*, Muriel Pichavant^*, Omid Akbari^*, Takahiro Yasumi^*, Paul B. Savage, Rosemarie H. DeKruyff^* and Dale T. Umetsu^3,*

^* Division of Immunology and Allergy, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115; Department of Internal Medicine, Division of Allergy and Asthma, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, South Korea; and Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602

Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation and by a central feature called airway hyperreactivity (AHR), development of which requires the presence of classical type I invariant NK T (iNKT) cells. Allergen-induced AHR, however, develops in β₂-microglobulin (β₂m)^–/– mice, which lack classical iNKT cells, suggesting that in some situations iNKT cells may be dispensable for the development of AHR. In contrast, our studies now suggest that a CD1d-restricted, NK1.1⁺ noninvariant TCR NKT cell population is present in β₂m^–/– mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of β₂m^–/– mice with anti-CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1-restricted NKT cells in these mice, which failed to respond to -galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a β₂m-independent form of CD1d. These results indicate that, although classical type I iNKT cells are normally required for the development of AHR, under different circumstances other NKT cell subsets, including nonclassical NKT cells, may substitute for classical iNKT cells and induce AHR.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants HL062348 and AI26322 from the National Institutes of Health, funds from the Bunning Food Allergy Project, and a research fund from Chonnam National University Research Institute of Medical Sciences (to Y.I.K.).

² Y.I.K. and H.Y.K. contributed equally to the completion of these studies.

³ Address correspondence and reprint requests to Dr. Dale T. Umetsu, Division of Immunology and Allergy, Karp Laboratories, Room 10127, One Blackfan Circle, Children’s Hospital Boston, Boston, MA 02115. E-mail address: dale.umetsu{at}childrens.harvard.edu

⁴ Abbreviations used in this paper: AHR, airway hyperreactivity; -GalCer, -galactosylceramide; BAL, bronchoalveolar lavage; β₂m, β₂-microgolubin; DN, double negative; WT, wild type; iNKT, invariant NKT; R_L, ling resistance.

This article has been cited by other articles:

				H. Y. Kim, M. Pichavant, P. Matangkasombut, Y. I. Koh, P. B. Savage, R. H. DeKruyff, and D. T. Umetsu The Development of Airway Hyperreactivity in T-bet-Deficient Mice Requires CD1d-Restricted NKT Cells J. Immunol., March 1, 2009; 182(5): 3252 - 3261. [Abstract] [Full Text] [PDF]