Nature Medicine9, 582 - 588 (2003)
Published online: 31 March 2003; | doi:10.1038/nm851
Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity
Omid Akbari1, Philippe Stock1, Everett Meyer1, Mitchell Kronenberg2, Stephane Sidobre2, Toshinori Nakayama3, Masaru Taniguchi3, Michael J. Grusby4, Rosemarie H. DeKruyff1
& Dale T. Umetsu1
1
Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, California, USA
2
Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, San Diego, California, USA
3
Graduate School of Medicine, Chiba University, Chiba, Japan
4
School of Public Health, Harvard University, Boston, Massachusetts, USA
Using natural killer T (NKT) cell−deficient mice, we show here that allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma, does not develop in the absence of V14i NKT cells. The failure of NKT cell−deficient mice to develop AHR is not due to an inability of these mice to produce type 2 T-helper (Th2) responses because NKT cell−deficient mice that are immunized subcutaneously at non-mucosal sites produce normal Th2-biased responses. The failure to develop AHR can be reversed by the adoptive transfer of tetramer-purified NKT cells producing interleukin (IL)-4 and IL-13 to Ja281-/- mice, which lack the invariant T-cell receptor (TCR) of NKT cells, or by the administration to Cd1d-/- mice of recombinant IL-13, which directly affects airway smooth muscle cells. Thus, pulmonary V14i NKT cells crucially regulate the development of asthma and Th2-biased respiratory immunity against nominal exogenous antigens. Therapies that target V14i NKT cells may be clinically effective in limiting the development of AHR and asthma.
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14i NKT cells. The failure of NKT cell−deficient mice to develop AHR is not due to an inability of these mice to produce type 2 T-helper (Th2) responses because NKT cell−deficient mice that are immunized subcutaneously at non-mucosal sites produce normal Th2-biased responses. The failure to develop AHR can be reversed by the adoptive transfer of tetramer-purified NKT cells producing interleukin (IL)-4 and IL-13 to Ja281-/- mice, which lack the invariant T-cell receptor (TCR) of NKT cells, or by the administration to Cd1d-/- mice of recombinant IL-13, which directly affects airway smooth muscle cells. Thus, pulmonary V
