title: Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity.
abstract: 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 V(alpha)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(alpha)14i NKT cells crucially regulate the development of asthma and Th2-biased respiratory immunity against nominal exogenous antigens. Therapies that target V(alpha)14i NKT cells may be clinically effective in limiting the development of AHR and asthma.
authors.affiliation: Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, California, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
authors.forename: Philippe
authors.initials: P
authors.lastname: Stock
authors.forename: Everett
authors.initials: E
authors.lastname: Meyer
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Stephane
authors.initials: S
authors.lastname: Sidobre
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Grusby
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: DeKruyff
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000485:Allergens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D018793:Interleukin-13; D015847:Interleukin-4