Cell Therapy for Prophylactic Tolerance in Immunoglobulin E-mediated Allergy.
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.


CONCLUSIONS
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.
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Ulrike
U
Baranyi
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Andreas M
AM
Farkas
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Karin
K
Hock
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Benedikt
B
Mahr
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Physiology and Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Birgit
B
Linhart
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Martina
M
Gattringer
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Physiology and Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Margit
M
Focke-Tejkl
Research Center Borstel, Clinical and Molecular Allergology, Borstel, Germany.
Arnd
A
Petersen
Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
Fritz
F
Wrba
Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria.
Thomas
T
Rülicke
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Physiology and Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Rudolf
R
Valenta
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: Thomas.Wekerle@meduniwien.ac.at.
Thomas
T
Wekerle
D000485:Allergens / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011058:Pollen / Q000276:immunology; D065129:Pre-Exposure Prophylaxis / Q000379:methods
D000485:Allergens; D007073:Immunoglobulin E
Allergen-specific tolerance induction; Allergy prophylaxis; B-cell tolerance; Cell-based therapy; T-cell tolerance