title: Activation of nonclassical CD1d-restricted NK T cells induces airway hyperreactivity in beta 2-microglobulin-deficient mice.
abstract: 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 beta(2)-microglobulin (beta(2)m)(-/-) 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 beta(2)m(-/-) mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of beta(2)m(-/-) 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 alpha-galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a beta(2)m-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.
authors.affiliation: 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.
authors.forename: Youngil I
authors.initials: YI
authors.lastname: Koh
authors.affiliation: Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
authors.forename: Everett H
authors.initials: EH
authors.lastname: Meyer
authors.affiliation: Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.affiliation: Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
authors.affiliation: Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.affiliation: Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: DeKruyff
authors.affiliation: Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics*
chemical_list: D055610:Antigens, CD1d; D001613:beta 2-Microglobulin
references.citation: J Immunol. 2004 Sep 1;173(5):3112-8
references.pmid: 15322171
references.citation: J Immunol. 1998 Aug 15;161(4):1962-9
references.pmid: 9712067
references.citation: N Engl J Med. 2006 Mar 16;354(11):1117-29
references.pmid: 16540612
references.citation: J Immunol. 1998 Mar 15;160(6):2649-54
references.pmid: 9510163
references.citation: J Exp Med. 2008 May 12;205(5):1037-48
references.pmid: 18411341
references.citation: Thorax. 1998 Nov;53(11):992-8
references.pmid: 10193402
references.citation: J Biol Chem. 1999 Apr 2;274(14):9289-95
references.pmid: 10092605
references.citation: Annu Rev Immunol. 1999;17:255-81
references.pmid: 10358759
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2782-7
references.pmid: 16478801
references.citation: J Exp Med. 2005 Dec 19;202(12):1623-6
references.pmid: 16365145
references.citation: J Clin Invest. 2004 May;113(10):1490-7
references.pmid: 15146247
references.citation: J Immunol. 1998 Aug 15;161(4):1710-7
references.pmid: 9712035
references.citation: Nature. 2005 Mar 24;434(7032):525-9
references.pmid: 15791258
references.citation: Am J Respir Crit Care Med. 1998 Jan;157(1):4-9
references.pmid: 9445270
references.citation: Nat Rev Immunol. 2006 Dec;6(12):953-8
references.pmid: 17068504
references.citation: J Immunol. 2003 Aug 15;171(4):1637-41
references.pmid: 12902459
references.citation: J Immunol. 2004 May 15;172(10):6115-22
references.pmid: 15128797
references.citation: J Clin Invest. 1999 Jan;103(2):175-83
references.pmid: 9916129
references.citation: Nat Med. 2003 May;9(5):582-8
references.pmid: 12669034
references.citation: J Exp Med. 2000 Sep 4;192(5):741-54
references.pmid: 10974039
references.citation: J Exp Med. 1999 Feb 1;189(3):553-62
references.pmid: 9927517
references.citation: Nat Med. 2008 Jun;14(6):633-40
references.pmid: 18488036
references.citation: J Exp Med. 2002 Mar 4;195(5):637-41
references.pmid: 11877486
references.citation: Immunity. 2002 Apr;16(4):583-94
references.pmid: 11970881
references.citation: J Exp Med. 1995 Oct 1;182(4):993-1004
references.pmid: 7561702
references.citation: J Exp Med. 2007 May 14;204(5):995-1001
references.pmid: 17470641
references.citation: J Immunol. 1999 Sep 1;163(5):2592-600
references.pmid: 10452998
references.citation: J Allergy Clin Immunol. 2007 Nov;120(5 Suppl):S94-138
references.pmid: 17983880
references.citation: Nature. 1984 Apr 12-18;308(5960):642-5
references.pmid: 6369147
references.citation: Science. 1994 Jul 8;265(5169):259-62
references.pmid: 7517575
references.citation: J Exp Med. 1996 Oct 1;184(4):1295-304
references.pmid: 8879201
references.citation: J Exp Med. 1996 Oct 1;184(4):1507-12
references.pmid: 8879221
references.citation: J Exp Med. 2005 Dec 19;202(12):1627-33
references.pmid: 16365146
references.citation: J Immunol. 2008 Apr 15;180(8):5167-71
references.pmid: 18390697
references.citation: Nat Immunol. 2000 Dec;1(6):515-20
references.pmid: 11101874
references.citation: J Exp Med. 2008 Feb 18;205(2):385-93
references.pmid: 18250191