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

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 he...

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Veröffentlicht in:European journal of immunology 2013-09, Vol.43 (9), p.2451-2460
Hauptverfasser: Baranyi, Ulrike, Gattringer, Martina, Farkas, Andreas M., Hock, Karin, Pilat, Nina, Iacomini, John, Valenta, Rudolf, Wekerle, Thomas
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Sprache:eng
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Zusammenfassung: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 TH1‐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.
ISSN:0014-2980
1521-4141
1521-4141
DOI:10.1002/eji.201243277