Activation of nonclassical CD1d-restricted NK T cells induces airway hyperreactivity in beta 2-microglobulin-deficient mice.
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.
Koh
Youngil I
YI
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.
Kim
Hye Young
HY
Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
Meyer
Everett H
EH
Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
Pichavant
Muriel
M
Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
Akbari
Omid
O
Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
Yasumi
Takahiro
T
Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
Savage
Paul B
PB
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602.
DeKruyff
Rosemarie H
RH
Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
Umetsu
Dale T
DT
Division of Immunology and Allergy, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115.
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*
D055610:Antigens, CD1d; D001613:beta 2-Microglobulin
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