title: Intravenous injection of a D1 protein of the Smith proteins postpones murine lupus and induces type 1 regulatory T cells.
abstract: T cells that recognize nucleoproteins are required for the production of anti-dsDNA Abs involved in lupus development. SmD1 83-119 (a D1 protein of the Smith (Sm) proteins, part of small nuclear ribonucleoprotein) was recently shown to provide T cell help to anti-dsDNA Abs in the NZB/NZW model of lupus. Using this model in the present study, we showed that high dose tolerance to SmD1 (600-1000 microg i.v. of SmD1(83-119) peptide/mo) delays the production of autoantibodies, postpones the onset of lupus nephritis as confirmed by histology, and prolongs survival. Tolerance to SmD1 83-119 was adoptively transferred by CD90+ T cells, which also reduce T cell help for autoreactive B cells in vitro. One week after SmD1 83-119 tolerance induction in prenephritic mice, we detected cytokine changes in cultures of CD90+ T and B220+ B cells with decreased IFN-gamma and IL-4 expression and an increase in TGFbeta. Increased frequencies of regulatory IFN-gamma+ and IL10+ CD4+ T cells were later detected. Such regulatory IL-10+/IFN-gamma+ type 1 regulatory T cells prevented autoantibody generation and anti-CD3-induced proliferation of naive T cells. In conclusion, these results indicate that SmD1 83-119 peptide may play a dominant role in the activation of helper and regulatory T cells that influence autoantibody generation and murine lupus.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany. gabriela.riemekasten@charite.de
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.forename: Dirk
authors.initials: D
authors.lastname: Langnickel
authors.forename: Philipp
authors.initials: P
authors.lastname: Enghard
authors.forename: Reinmar
authors.initials: R
authors.lastname: Undeutsch
authors.forename: Jens
authors.initials: J
authors.lastname: Humrich
authors.forename: Fanny M
authors.initials: FM
authors.lastname: Ebling
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
authors.forename: Tiina
authors.initials: T
authors.lastname: Humaljoki
authors.forename: Hans
authors.initials: H
authors.lastname: Neumayer
authors.forename: Gerd-R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000378:metabolism; D001324:Autoantigens / Q000008:administration & dosage* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance; D007275:Injections, Intravenous; D008181:Lupus Nephritis / Q000276:immunology* / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000008:administration & dosage* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D055517:snRNP Core Proteins
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D016207:Cytokines; D006131:Growth Inhibitors; D010446:Peptide Fragments; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins