,
,
,
,
,
,
,
,
,
,
,
1Current address: Cardiac Surgery Laboratory, Department of Surgery.
2RV and TW are co-senior authors.
Open Access
Article Info
Highlights
- •Avoidance of IgE-mediated allergy is established by development of a tolerogenic cell-based protocol.
- •Transplantation of syngeneic allergen-bearing bone marrow cells into recipients leads to tolerance towards the introduced allergen.
- •Prevention of T-and B-cell responses and allergic asthma is induced by cell transfer with non-toxic pretreatment.
IgE-mediated allergy affects about 30% of the population in industrialized countries. To prevent allergy we developed a cell-based protocol with the concept to modify body's own cells to express an allergen and to reinfuse those modified cells. This concept leads to avoidance of allergic reactions after allergen contact such as specific IgE production and the development of allergic asthma. This is demonstrated in a syngeneic model in mice (i.e. autologous in human) by transplanting bone marrow cells of a unique allergen-expressing transgenic mouse into pretreated recipients.
Abstract
Background
Therapeutic strategies for the prophylaxis of IgE-mediated allergy remain an unmet medical need. Cell therapy is an emerging approach with high potential for preventing and treating immunological diseases.
We aimed to develop a cell-based therapy inducing permanent allergen-specific immunological tolerance for preventing IgE-mediated allergy.
Methods
Wild-type mice were treated with allergen-expressing bone marrow cells under a short course of tolerogenic immunosuppression (mTOR inhibition and costimulation blockade). Bone marrow was retrieved from a novel transgenic mouse ubiquitously expressing the major grass pollen allergen Phl p 5 as a membrane-anchored protein (BALB/c-Tg[Phlp5-GFP], here mPhl p 5). After transplantation recipients were IgE-sensitized at multiple time points with Phl p 5 and control allergen.
Results
Mice treated with mPhl p 5 bone marrow did not develop Phl p 5-specific IgE (or other isotypes) despite repeated administration of the allergen, while mounting and maintaining a strong humoral response towards the control allergen. Notably, Phl p 5-specific T cell responses and allergic airway inflammation were also completely prevented. Interestingly allergen-specific B cell tolerance was maintained independent of Treg functions indicating deletional tolerance as underlying mechanism.
Conclusion
This proof-of-concept study demonstrates that allergen-specific immunological tolerance preventing occurrence of allergy can be established through a cell-based therapy employing allergen-expressing leukocytes.
No comments:
Post a Comment