title: 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.affiliation: Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Baranyi
authors.forename: Martina
authors.initials: M
authors.lastname: Gattringer
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Farkas
authors.forename: Karin
authors.initials: K
authors.lastname: Hock
authors.forename: Nina
authors.initials: N
authors.lastname: Pilat
authors.forename: John
authors.initials: J
authors.lastname: Iacomini
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.forename: Thomas
authors.initials: T
authors.lastname: Wekerle
mesh_terms: D016475:3T3 Cells; D000485:Allergens / Q000096:biosynthesis / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology* / Q000821:virology; D016026:Bone Marrow Transplantation / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D002678:Chimera / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D054243:Vesicular Stomatitis / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E
keywords: Allergy; B-cell tolerance; Molecular chimerism; Phl p 5; T-cell tolerance