title: Red blood cells as innovative antigen carrier to induce specific immune tolerance.
abstract: The route of administration, the dose of antigen as well as the type of antigen-presenting cells (APCs) targeted are important factors to induce immune tolerance. Despite encouraging results obtained in animal models, intravenous injection of soluble antigen is unsuccessful in human clinical trials on autoimmune disease due to inefficient antigen delivery. To improve antigen delivery, we used mouse red blood cells (RBCs) as antigen vehicles to specifically target APCs which are responsible for removal of senescent RBCs after phagocytosis. In this study, we demonstrated that antigen-delivery by RBCs induced a strong decrease in the humoral response compared with the ovalbumin (OVA) free form in mice. In addition, OVA-loaded RBC treated with [bis(sulphosuccinimidyl)] suberate (BS3), a chemical compound known to enhance RBC phagocytosis, induced an inhibition of antigen-specific T cell responses and an increase in the percentage of regulatory T cells. The state of tolerance induced is long lasting, antigen-specific and sufficiently robust to withstand immunization with antigen mixed with cholera toxin adjuvant. This RBC strategy, which does not abolish the immune system, constitutes an attractive approach for induction of tolerance compared to systemic immunosuppressant therapies already in use.
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Cremel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guérin
authors.forename: Françoise
authors.initials: F
authors.lastname: Horand
authors.forename: Alice
authors.initials: A
authors.lastname: Banz
authors.forename: Yann
authors.initials: Y
authors.lastname: Godfrin
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D061207:Calcium Ionophores / Q000494:pharmacology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004337:Drug Carriers; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D013388:Succinimides / Q000494:pharmacology
chemical_list: D000941:Antigens; D061207:Calcium Ionophores; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D007074:Immunoglobulin G; D013388:Succinimides; D010047:Ovalbumin; C035760:bis(sulfosuccinimidyl)suberate