title: Cutting edge: invariant V alpha 14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model.
abstract: Airway hyperreactivity (AHR), eosinophilic inflammation with a Th2-type cytokine profile, and specific Th2-mediated IgE production characterize allergic asthma. In this paper, we show that OVA-immunized Jalpha18(-/-) mice, which are exclusively deficient in the invariant Valpha14(+) (iValpha14), CD1d-restricted NKT cells, exhibit impaired AHR and airway eosinophilia, decreased IL-4 and IL-5 production in bronchoalveolar lavage fluid, and reduced OVA-specific IgE compared with wild-type (WT) littermates. Adoptive transfer of WT iValpha14 NKT cells fully reconstitutes the capacity of Jalpha18(-/-) mice to develop allergic asthma. Also, specific tetramer staining shows that OVA-immunized WT mice have activated (CD69(+)) iValpha14 NKT cells. Importantly, anti-CD1d mAb treatment blocked the ability of iValpha14 T cells to amplify eosinophil recruitment to airways, and both Th2 cytokine and IgE production following OVA challenge. In conclusion, these findings clearly demonstrate that iValpha14 NKT cells are required to participate in allergen-induced Th2 airway inflammation through a CD1d-dependent mechanism.
authors.affiliation: Centre National de la Recherche Scientifique Formation de Recherche en Evolution 2444, Paris V, Hôpital Necker, Paris, France.
authors.forename: Mariette
authors.initials: M
authors.lastname: Lisbonne
authors.forename: Séverine
authors.initials: S
authors.lastname: Diem
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Castro Keller
authors.forename: Jean
authors.initials: J
authors.lastname: Lefort
authors.forename: Luiza M
authors.initials: LM
authors.lastname: Araujo
authors.forename: Patricia
authors.initials: P
authors.lastname: Hachem
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Fourneau
authors.forename: Stéphane
authors.initials: S
authors.lastname: Sidobre
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Masuru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Peter
authors.initials: P
authors.lastname: Van Endert
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.forename: Philip
authors.initials: P
authors.lastname: Askenase
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
authors.forename: B Boris
authors.initials: BB
authors.lastname: Vargaftig
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
authors.forename: Maria C
authors.initials: MC
authors.lastname: Leite-de-Moraes
mesh_terms: D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D016056:Immunodominant Epitopes / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D016056:Immunodominant Epitopes; D015848:Interleukin-5; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin