Molecular chimerism in IgE-mediated allergy: B-and T-cell tolerance toward highly immunogenic exogenous antigens

Specific immunotherapy is the only curative treatment currently available for IgE-mediated allergy and preventive strategies are lacking altogether. We have recently reported that molecular chimerism induces durable tolerance in experimental models of allergy, thus potentially providing a new approach for the treatment and prevention of allergic diseases. Molecular chimerism is a gene-therapy approach for tolerance induction toward defined disease-causing antigens. In proof-of-concept studies, we introduced a clinically relevant grass pollen allergen into hematopoietic stem cells and transplanted those modified cells into preconditioned syngeneic mice. Long-lasting and robust tolerance toward the allergen was achieved. In our most recent studies published in Clinical and Experimental Allergy we demonstrated that milder, non-myeloablative conditioning is sufficient to induce tolerance. Our results revealed that, in contrast to other rodent models of chimerism, persistent microchimerism suffices to induce lasting tolerance at the T cell, B cell and effector cell levels in IgE-mediated allergy. This article addendum provides a summary of the recent paper and its implications.