title: B lymphocytes treated in vitro with antigen coupled to cholera toxin B subunit induce antigen-specific Foxp3(+) regulatory T cells and protect against experimental autoimmune encephalomyelitis.
abstract: The ability of activated B cells to protect against various experimental autoimmune or allergic diseases makes them attractive for use in cell-based therapies. We describe an efficient way to generate B cells with strong suppressive functions by incubating naive B cells with a relevant Ag conjugated to cholera toxin B subunit (CTB). This allows most B cells, irrespective of BCR, to take up and present Ag and induces their expression of latency-associated polypeptide (LAP)/TGF-β and after adoptive transfer also their production of IL-10. With OVA as model Ag, when naive T cells were cocultured in vitro with B cells pretreated with OVA conjugated to CTB (OVA/CTB) Ag-specific CD4(+) Foxp3 regulatory T (Treg) cells increased >50-fold. These cells effectively suppressed CD25(-)CD4(+) effector T (Teff) cells in secondary cultures. Adoptive transfer of OVA/CTB-treated B cells to mice subsequently immunized with OVA in CFA induced increase in Foxp3 Treg cells together with suppression and depletion of Teff cells. Likewise, adoptive transfer of B cells pulsed with myelin oligodendrocyte glycoprotein peptide(35-55) (MOGp) conjugated to CTB increased the number of Treg cells, suppressed MOGp-specific T cell proliferation and IL-17 and IFN-γ production, and prevented the development of experimental autoimmune encephalomyelitis. Similar effects were seen when B cells were given "therapeutically" to mice with early-stage experimental autoimmune encephalomyelitis. Our results suggest that B cells pulsed in vitro with relevant Ag/CTB conjugates may be used in cell therapy to induce Ag-specific suppression of autoimmune disease.
authors.affiliation: University of Gothenburg Vaccine Research Institute, Sahlgrenska Academy at the University of Gothenburg, SE-405 30, Göteborg, Sweden. jia-bin.sun@microbio.gu.se
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Sun
authors.forename: Cecil
authors.initials: C
authors.lastname: Czerkinsky
authors.forename: Jan
authors.initials: J
authors.lastname: Holmgren
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006023:Glycoproteins / Q000276:immunology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006023:Glycoproteins; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma; D010047:Ovalbumin; D002772:Cholera Toxin