title: Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics.
abstract: Atopic allergic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Previous reports have suggested an important role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen challenge. However, human allergen-specific lines and clones were reported to be costimulation independent. We therefore examined CD80 and CD86 dependence of allergen-induced T cell proliferation and cytokine production in peripheral blood and bronchoalveolar lavage from atopic asthmatic subjects and controls. Both allergen-induced proliferation and IL-5 production from PBMC were inhibited by CTLA4-Ig fusion protein and anti-CD86, but not anti-CD80 mAbs. When allergen-specific CD4+ T cell lines from peripheral blood were examined, proliferation and cytokine production were found to be independent of CD80 or CD86 costimulation. However, when cells obtained directly from the airways were examined, allergen-induced proliferation of bronchoalveolar lavage T cells from atopic asthmatic subjects was inhibited by anti-CD86 but not anti-CD80. In addition, bronchoalveolar lavage-adherent cells from asthmatic, but not control subjects showed APC activity to autologous T cells. This was also inhibited by anti-CD86 but not anti-CD80. Thus allergen-induced T cell activation and IL-5 production in the airway in asthmatic subjects is susceptible to blockade by agents interfering with costimulation via CD86, and this may hold therapeutic potential in asthma.
authors.affiliation: Allergy and Clinical Immunology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Larché
authors.forename: S J
authors.initials: SJ
authors.lastname: Till
authors.forename: B M
authors.initials: BM
authors.lastname: Haselden
authors.forename: J
authors.initials: J
authors.lastname: North
authors.forename: J
authors.initials: J
authors.lastname: Barkans
authors.forename: C J
authors.initials: CJ
authors.lastname: Corrigan
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
authors.forename: D S
authors.initials: DS
authors.lastname: Robinson
mesh_terms: D000069594:Abatacept; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology; D000943:Antigens, Differentiation / Q000494:pharmacology; D001249:Asthma / Q000276:immunology*; D051940:B7-2 Antigen; D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D000069594:Abatacept; D017493:Leukocyte Common Antigens