Activation of Nonclassical Cd1d-Restricted Nk T Cells Induces Airway Hyperreactivity in 2-Microglobulin-Deficient Mice

Koh, Y.I.; Kim, H.Y.; Meyer, E.H.; Pichavant, M.; Akbari, O.; Yasumi, T.; Savage, P.B.; DeKruyff, R.H.; Umetsu, D.T.

The Journal of Immunology 181(7): 4560-4569

2008


DOI: 10.4049/jimmunol.181.7.4560
Accession: 068491168

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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.