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In contrast to specific B cells, human basophils are unaffected by the toxic activity of an allergen toxin due to lack of internalization of immunoglobulin E-bound allergen

 
: Wicklein, D.; Stöcker, M.; Klockenbring, T.; Huhn, M.; Wodrich, M.; Haas, H.; Becker, W.-M.; Barth, S.; Petersen, A.

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Clinical & experimental allergy 36 (2006), No.4, pp.531-542
ISSN: 0954-7894
ISSN: 0960-2178
English
Journal Article
Fraunhofer IME ()

Abstract
Background Specific immunotherapy is the only curative therapy for type I allergies and the alarming increase in allergy prevalence emphasizes the need for additional/alternative strategies for curative treatment. Allergen toxins (AT), fusion products of an allergen with an apoptosis inducing cytotoxin, are a new kind of immunotoxin. Objective AT should allow allergen-specific targeting and elimination of allergy-relevant cells, with B cells being the primary target. An important question is the fate of the effector cells, e.g. mast cells and basophils, which carry allergen-specific IgE: the immunotoxin might even prove to be harmful. Methods We established a reliable in vitro B cell model (using two mouse hybridoma cell lines) for testing specificity and toxicity of P5-ETA', a fusion protein of the major timothy grass pollen allergen Phl p 5b and truncated Pseudomonas Exotoxin A. In a second step, we investigated the impact of the AT on human basophils. Results P5-ETA' reliably eliminated Phl p 5-specific cells in the in vitro B cell model, leaving unspecific B cells unharmed. Human basophils of grass pollen allergic donors specifically bound P5-ETA', released IL-4 and up-regulated the activation marker CD203c, but were not subject to the toxic effect because of lack of internalization of IgE-bound allergen. Conclusion According to our data, basophils are pure effector cells in the context of IgE-bound allergen and not involved in classical antigen presentation.

: http://publica.fraunhofer.de/documents/N-59999.html