The site of allergen expression in hematopoietic cells determines the degree and quality of tolerance induced through molecular chimerism.

Abstract

The transplantation of allergens (e.g. Phl p 5 or Bet v 1) expressed on BM cells as membrane-anchored full-length proteins leads to permanent tolerance at the T-cell, B-cell, and effector-cell levels. Since the exposure of complete allergens bears the risk of inducing anaphylaxis, we investigated here whether expression of Phl p 5 in the cytoplasm (rather than on the cell surface) is sufficient for tolerance induction. Transplantation of BALB/c BM retrovirally transduced to express Phl p 5 in the cytoplasm led to stable and durable molecular chimerism in syngeneic recipients (∼20% chimerism at 6 months). Chimeras showed allergen-specific T-cell hyporesponsiveness. Further, Phl p 5-specific TH 1-dependent humoral responses were tolerized in several chimeras. Surprisingly, Phl p 5-specific IgE and IgG1 levels were significantly reduced but still detectable in sera of chimeric mice, indicating incomplete B-cell tolerance. No Phl p 5-specific sIgM developed in cytoplasmic chimeras, which is in marked contrast to mice transplanted with BM expressing membrane-anchored Phl p 5. Thus, the expression site of the allergen substantially influences the degree and quality of tolerance achieved with molecular chimerism in IgE-mediated allergy.

• Authors: Ulrike Baranyi, Martina Gattringer, Andreas M Farkas, Karin Hock, Nina Pilat, John Iacomini, Rudolf Valenta, Thomas Wekerle
• Journal: European journal of immunology (Eur J Immunol) Vol. 43 Issue 9 Pg. 2451-60 (Sep 2013) ISSN: 1521-4141 [Electronic] Germany
• PMID: 23765421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.

Chemical References

• Allergens
• Antigens, Plant
• Immunoglobulin G
• Immunoglobulin M
• Phl p V protein, Phleum pratense
• Plant Proteins
• Bet v 1 allergen, Betula
• Immunoglobulin E

Topics

• 3T3 Cells
• Allergens (biosynthesis, immunology)
• Animals
• Antigens, Plant (immunology)
• B-Lymphocytes (immunology)
• Bone Marrow Cells (immunology, virology)
• Bone Marrow Transplantation (immunology)
• Cell Line
• Cell Proliferation
• Chimera (immunology)
• Female
• Hypersensitivity (immunology)
• Immune Tolerance
• Immunoglobulin E (blood, immunology)
• Immunoglobulin G (blood, immunology)
• Immunoglobulin M (blood, immunology)
• Mice
• Mice, Inbred BALB C
• Plant Proteins (immunology)
• T-Lymphocytes (immunology)
• Vesicular Stomatitis (immunology)
• Vesicular stomatitis Indiana virus (immunology)