title: Identification and characterization of SmD183-119-reactive T cells that provide T cell help for pathogenic anti-double-stranded DNA antibodies.
abstract: OBJECTIVE
  The C-terminal peptide of amino acids 83-119 of the SmD1 protein is a target of the autoimmune response in human and murine lupus. This study was undertaken to test the hypothesis that SmD1(83-119)-reactive T cells play a crucial role in the generation of pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies.
  
  
  METHODS
  Splenic or lymph node T cells derived from unmanipulated as well as SmD1(83-119)-immunized NZB/NZW mice were analyzed in vitro by enzyme-linked immunospot (ELISpot) assay to determine T cell help for anti-dsDNA generation induced by the SmD1(83-119) peptide. Cytokines expressed by these T cells were measured by ELISpot assay, enzyme-linked immunosorbent assay, and flow cytometry. SmD1(83-119)- and ovalbumin-specific T cell lines were generated and characterized.
  
  
  RESULTS
  The SmD1(83-119) peptide, but not the control peptides, significantly increased the in vitro generation of anti-dsDNA antibodies in cultures from unmanipulated NZB/NZW mice. Interferon-gamma (IFNgamma), interleukin-2 (IL-2), IL-4, transforming growth factor beta, and IL-10 production increased in response to the peptide in young mice; only IFNgamma and IL-2 were increased in older, diseased mice. Activation of SmD1(83-119)-reactive T cells by immunization of NZB/NZW mice resulted in elevated anti-dsDNA synthesis and, later, increased antibodies to SmD1(83-119). Most cells in SmD1(83-119)-specific CD4+ T cell lines helping both antibodies had increased intracellular expression of IFNgamma, and most expressed both IFNgamma and IL-4.
  
  
  CONCLUSIONS
  The SmD1(83-119) peptide plays an important role in generating T cell help for autoantibodies, including anti-dsDNA, and activates different subsets of T cells as defined by distinct cytokine expression. This peptide is an interesting target structure for the modulation of autoreactive T cells, and its characterization may contribute to our understanding of the role of autoantigen-reactive T cells in the pathogenesis of SLE.
authors.affiliation: University of California, Los Angeles, USA. gabriela.riemekasten@charite.de
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.forename: Dirk
authors.initials: D
authors.lastname: Langnickel
authors.forename: Fanny M
authors.initials: FM
authors.lastname: Ebling
authors.forename: George
authors.initials: G
authors.lastname: Karpouzas
authors.forename: Jatinderpal
authors.initials: J
authors.lastname: Kalsi
authors.forename: Gunda
authors.initials: G
authors.lastname: Herberth
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
authors.forename: Peter
authors.initials: P
authors.lastname: Henklein
authors.forename: Sven
authors.initials: S
authors.lastname: Langer
authors.forename: Gerd-R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000032:analysis; D004247:DNA / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007114:Immunization; D066298:In Vitro Techniques; D051379:Mice; D008814:Mice, Inbred NZB; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010950:Plasma Cells / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D055517:snRNP Core Proteins
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D010446:Peptide Fragments; D017411:Ribonucleoproteins, Small Nuclear; C526409:SNRPD1 protein, human; D055517:snRNP Core Proteins; D004247:DNA