Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy.

Content Provider	Semantic Scholar
Author	Linhart, Birgit Bigenzahn, Sinda Hartl, Arnulf Lupinek, Christian Thalhamer, Josef Valenta, Rudolf Wekerle, Thomas
Copyright Year	2007
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.
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Alternate Webpage(s)	http://www.jimmunol.org/content/jimmunol/178/6/3924.full.pdf
PubMed reference number	17339493v1
Volume Number	178
Issue Number	6
Journal	Journal of immunology
Language	English
Access Restriction	Open
Subject Keyword	Allergens Basophils Cellular Phone Drug Allergy Hay fever Hypersensitivity Immunoglobulin A Immunoglobulin E Leukemia, B-Cell Mediator brand of benfluorex hydrochloride Phleum Sensitization (observable entity) T-Lymphocyte abatacept leukemia
Content Type	Text
Resource Type	Article