title: Histone peptide-induced nasal tolerance: suppression of murine lupus.
abstract: Induced mucosal tolerance has been shown to be beneficial in preventing or treating a number of murine and human autoimmune disorders. However, this particular form of therapy has not been thoroughly tested in systemic lupus erythematosus. In this study, we investigated the conditions for induction of nasal tolerance using a histone peptide named H471 expressing a dominant T cell epitope in the histone protein H4 of mononucleosome in lupus-prone SNF(1) female mice. We also tested the effect of chronic peptide nasal treatment on the development of autoimmune reactivities in these mice. Results demonstrated that a dose-dependent nasal tolerance to peptide H471 can be achieved before or after peptide sensitization in SNF(1) mice. In addition, tolerance to mononucleosomes was induced by nasal instillation of SNF(1) mice with H471. This was accompanied by an increase in IL-10 and suppression of IFN-gamma production by lymph node cells. Suppression of Th1-type cytokines was also observed in SNF(1) mice that were nasally administered with H471 before intradermal injection with the peptide. Finally, chronic nasal instillation of mice with the H471 peptide not only suppressed the development of autoantibodies, but also altered the severity of glomerulonephritis in lupus-prone SNF(1) mice.
authors.affiliation: Infection and Immunity Research Group, Division of Life Sciences, King's College London, London, United Kingdom. henry.wu@kcl.ac.uk
authors.forename: Henry Yim
authors.initials: HY
authors.lastname: Wu
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Ward
authors.forename: Norman A
authors.initials: NA
authors.lastname: Staines
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000517:prevention & control; D006657:Histones / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis / Q000145:classification; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology; D007271:Injections, Intradermal; D008181:Lupus Nephritis / Q000276:immunology* / Q000517:prevention & control*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology*; D009707:Nucleosomes / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D006657:Histones; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D009707:Nucleosomes; D010446:Peptide Fragments