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Baranyi, U; Linhart, B; Pilat, N; Gattringer, M; Bagley, J; Muehlbacher, F; Iacomini, J; Valenta, R; Wekerle, T.
Tolerization of a type I allergic immune response through transplantation of genetically modified hematopoietic stem cells.
J Immunol. 2008; 180(12):8168-8175 [OPEN ACCESS]
Web of Science PubMed PUBMED Central

 

Authors Med Uni Graz:
Baranyi Ulrike
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Number of Figures: 6
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Abstract:
Allergy represents a hypersensitivity disease that affects >25% of the population in industrialized countries. The underlying type I allergic immune reaction occurs in predisposed atopic individuals in response to otherwise harmless Ags (i.e., allergens) and is characterized by the production of allergen-specific IgE, an allergen-specific T cell response, and the release of biologically active mediators such as histamine from mast cells and basophils. Regimens permanently tolerizing an allergic immune response still need to be developed. We therefore retrovirally transduced murine hematopoietic stem cells to express the major grass pollen allergen Phl p 5 on their cell membrane. Transplantation of these genetically modified hematopoietic stem cells led to durable multilineage molecular chimerism and permanent immunological tolerance toward the introduced allergen at the B cell, T cell, and effector cell levels. Notably, Phl p 5-specific serum IgE and IgG remained undetectable, and T cell nonresponsiveness persisted throughout follow-up (40 wk). Besides, mediator release was specifically absent in in vitro and in vivo assays. B cell, T cell, and effector cell responses to an unrelated control allergen (Bet v 1) were unperturbed, demonstrating specificity of this tolerance protocol. We thus describe a novel cell-based strategy for the prevention of allergy.
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Allergens - administration and dosage Allergens - genetics Allergens - immunology
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Antigens, Plant -
Betula - genetics Betula - immunology
Bone Marrow Transplantation - immunology Bone Marrow Transplantation - methods
Female -
Hematopoietic Stem Cell Transplantation - methods
Hypersensitivity - classification Hypersensitivity - genetics Hypersensitivity - immunology
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Phleum - genetics Phleum - immunology
Plant Proteins - administration and dosage Plant Proteins - genetics Plant Proteins - immunology
Pollen - genetics Pollen - immunology
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Transduction, Genetic -
Transplantation Conditioning -

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