title: Allergen-induced airway hyperreactivity is diminished in CD81-deficient mice.
abstract: We demonstrated previously that CD81(-/-) mice have an impaired Th2 response. To determine whether this impairment affected allergen-induced airway hyperreactivity (AHR), CD81(-/-) BALB/c mice and CD81(+/+) littermates were sensitized i.p. and challenged intranasally with OVA. Although wild type developed severe AHR, CD81(-/-) mice showed normal airway reactivity and reduced airway inflammation. Nevertheless, OVA-specific T cell proliferation was similar in both groups of mice. Analysis of cytokines secreted by the responding CD81(-/-) T cells, particularly those derived from peribronchial draining lymph nodes, revealed a dramatic reduction in IL-4, IL-5, and IL-13 synthesis. The decrease in cytokine production was not due to an intrinsic T cell deficiency because naive CD81(-/-) T cells responded to polyclonal Th1 and Th2 stimulation with normal proliferation and cytokine production. Moreover, there was an increase in T cells and a decrease in B cells in peribronchial lymph nodes and in spleens of immunized CD81(-/-) mice compared with wild-type animals. Interestingly, OVA-specific Ig levels, including IgE, were similar in CD81(-/-) and CD81(+/+) mice. Thus, CD81 plays a role in the development of AHR not by influencing Ag-specific IgE production but by regulating local cytokine production.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: J
authors.initials: J
authors.lastname: Deng
authors.forename: V P
authors.initials: VP
authors.lastname: Yeung
authors.forename: D
authors.initials: D
authors.lastname: Tsitoura
authors.forename: R H
authors.initials: RH
authors.lastname: DeKruyff
authors.forename: D T
authors.initials: DT
authors.lastname: Umetsu
authors.forename: S
authors.initials: S
authors.lastname: Levy
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001402:B-Lymphocytes / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004802:Eosinophilia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009077:Mucins / Q000096:biosynthesis; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013045:Species Specificity; D013154:Spleen / Q000473:pathology; D060225:Tetraspanin 28; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D015703:Antigens, CD; C554799:Cd81 protein, mouse; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D009077:Mucins; D060225:Tetraspanin 28; D007073:Immunoglobulin E; D010047:Ovalbumin