Cell Therapy for Prophylactic Tolerance in Immunoglobulin E-mediated Allergy

Area of Science:

• Immunology
• Cell Therapy
• Allergy Research

Background:

• IgE-mediated allergy prophylaxis is a significant unmet medical need.
• Cell therapy presents a promising avenue for treating immunological diseases.
• Developing a permanent allergen-specific tolerance is key for allergy prevention.

Purpose of the Study:

• To develop and evaluate a cell-based therapy for inducing permanent allergen-specific immunological tolerance.
• To prevent IgE-mediated allergy using a novel cell therapy approach.

Main Methods:

• Wild-type mice received allergen-expressing bone marrow cells under tolerogenic immunosuppression (mTOR inhibition and costimulation blockade).
• Transgenic mice expressing the major grass pollen allergen Phl p 5 (mPhl p 5) were used to source bone marrow.
• Recipient mice were subsequently sensitized with Phl p 5 and a control allergen.

Main Results:

• Mice treated with mPhl p 5 bone marrow did not develop Phl p 5-specific IgE despite repeated allergen exposure.
• Phl p 5-specific T cell responses and allergic airway inflammation were completely prevented.
• Allergen-specific B cell tolerance was maintained independently of Treg functions, suggesting deletional tolerance.

Conclusions:

• This study provides proof-of-concept for a cell-based therapy to establish allergen-specific immunological tolerance.
• The developed therapy effectively prevents the occurrence of allergy.
• Allergen-expressing leukocytes can be utilized to induce lasting tolerance and prevent IgE-mediated allergic responses.