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Forschungsdatenbank PMU-SQQUID

Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy.
Linhart, B; Bigenzahn, S; Hartl, A; Lupinek, C; Thalhamer, J; Valenta, R; Wekerle, T;
J Immunol. 2007; 178(6):3924-3931
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Hartl Arnulf Josef

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 Phi 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.


Useful keywords (using NLM MeSH Indexing)

Abatacept

Allergens/immunology*

Animals

Antibodies, Monoclonal/immunology

Antibodies, Monoclonal/pharmacology*

CD40 Ligand/immunology*

Cell Line, Tumor

Disease Models, Animal

Hypersensitivity/drug therapy

Hypersensitivity/immunology*

Immunoconjugates/pharmacology*

Immunoglobulin E/immunology

Immunosuppressive Agents/pharmacology*

Mice

Mice, Inbred BALB C

Plant Proteins/immunology*

Rats

Th1 Cells/immunology

Th2 Cells/immunology