title: Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy.
abstract: Type I allergy is characterized by the development of an initial Th2-dependent allergen-specific IgE response, which is boosted upon a subsequent allergen encounter. Although the immediate symptoms of allergy are mainly IgE-mediated, allergen-specific T cell responses contribute to the late phase as well as to the chronic manifestations of allergy. This study investigates the potential of costimulation blockade with CTLA4Ig and an anti-CD154 mAb for modifying the allergic immune response to the major timothy grass pollen allergen Phl p 5 in a mouse model. BALB/c mice were treated with the costimulation blockers at the time of primary sensitization to the Phl p 5 allergen or at the time of a secondary allergen challenge. Costimulation blockade (CTLA4Ig plus anti-CD154 or anti-CD154 alone) at the time of sensitization prevented the development of allergen-specific IgE, IgM, IgG, and IgA responses compared with untreated but sensitized mice. However, costimulation blockade had no influence on established IgE responses in sensitized mice. Immediate-type reactions as analyzed by a rat basophil leukemia cell mediator release assay were only suppressed by early treatment but not by a costimulation blockade after sensitization. CTLA4Ig given alone failed to suppress both the primary and the secondary allergen-specific Ab responses. Allergen-specific T cell activation was suppressed in mice by early as well as by a late costimulation blockade, suggesting that IgE responses in sensitized mice are independent of T cell help. Our results indicate that T cell suppression alone without active immune regulation or a shifting of the Th2/Th1 balance is not sufficient for the treatment of established IgE responses in an allergy.
authors.affiliation: Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center of Physiology and Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Linhart
authors.forename: Sinda
authors.initials: S
authors.lastname: Bigenzahn
authors.forename: Arnulf
authors.initials: A
authors.lastname: Hartl
authors.forename: Christian
authors.initials: C
authors.lastname: Lupinek
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.forename: Thomas
authors.initials: T
authors.lastname: Wekerle
mesh_terms: D000069594:Abatacept; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D023201:CD40 Ligand / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D018796:Immunoconjugates / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000276:immunology*; D051381:Rats; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; C084984:PHLPII protein, Phleum pratense; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D023201:CD40 Ligand; D007073:Immunoglobulin E; D000069594:Abatacept