Persistent molecular microchimerism induces long-term tolerance towards a clinically relevant respiratory allergen

Area of Science:

• Immunology
• Allergy Research
• Stem Cell Transplantation

Background:

• Developing antigen-specific strategies for IgE-mediated allergy prevention remains a significant challenge.
• Previous research demonstrated successful allergy prevention through molecular chimerism and macrochimerism via syngeneic hematopoietic stem cell transplantation.
• The efficacy of lower levels of chimerism (microchimerism) for tolerance induction was yet to be determined.

Purpose of the Study:

• To investigate if microchimerism, induced by modified stem cell transplantation, is sufficient for preventing IgE-mediated allergy.
• To explore the potential for developing minimally toxic tolerance protocols based on microchimerism.

Main Methods:

• Bone marrow cells were genetically modified to express the grass pollen allergen Phl p 5.
• Modified cells were transplanted into non-myeloablated recipients, followed by repeated allergen immunization.
• Molecular chimerism, immune cell tolerance (T-cell, B-cell), and effector function were assessed.

Main Results:

• Transplantation resulted in persistent molecular chimerism, transitioning from macrochimerism to stable microchimerism over 11 months.
• Microchimerism was sufficient to induce B-cell tolerance, evidenced by the absence of Phl p 5-specific IgE.
• Both T-cell and effector-cell tolerance were successfully achieved in the treated recipients.

Conclusions:

• Persistent low-level molecular chimerism can effectively induce long-term tolerance in IgE-mediated allergies.
• These findings support the development of less toxic conditioning regimens for inducing low-level engraftment of genetically modified bone marrow for allergy treatment.