title: Protection against renal disease in (NZB x NZW)F(1) lupus-prone mice after somatic B cell gene vaccination with anti-DNA immunoglobulin consensus peptide.
abstract: OBJECTIVE
  Ig molecules contain epitopes that can induce T cell-mediated immune responses. B cells can process and present such epitopes and activate T cells. The purpose of the present study was to test our hypothesis that T cells that recognize an Ig consensus sequence presented by B cells will modulate lupus-like disease in mice.
  
  
  METHODS
  (NZB x NZW)F(1) (NZB/NZW) lupus mice received somatic B cell gene transfer of a DNA plasmid encoding a consensus sequence of T cell determinants of murine anti-DNA IgG or control plasmids. Treated animals were monitored for the production of antibody, the development of renal disease, and the phenotype, number, and function of T cells.
  
  
  RESULTS
  Treatment of mice with Ig consensus plasmid induced transforming growth factor beta-producing CD8+,CD28- T cells that suppressed the antigen-specific stimulation of CD4+ T cells in a cell-contact-independent manner, reduced antibody production, retarded the development of nephritis, and improved survival. Significantly, adoptive transfer of CD8+,CD28- T cells from protected mice into hypergammaglobulinemic NZB/NZW mice effectively protected the transferred mice from the development of renal disease.
  
  
  CONCLUSIONS
  Gene expression of anti-DNA Ig consensus sequence induces immunoregulatory T cells that delay the development of lupus nephritis by suppressing hypergammaglobulinemia and renal disease.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrera
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Marta
authors.initials: M
authors.lastname: Rizzi
authors.forename: Marissa
authors.initials: M
authors.lastname: Anderson
authors.forename: John
authors.initials: J
authors.lastname: Fitzgerald
authors.forename: Enrico
authors.initials: E
authors.lastname: Millo
authors.forename: Francesco
authors.initials: F
authors.lastname: Indiveri
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.forename: Gilberto
authors.initials: G
authors.lastname: Filaci
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016384:Consensus Sequence; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D018014:Gene Transfer Techniques; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008181:Lupus Nephritis / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008814:Mice, Inbred NZB; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000974:Antibodies, Antinuclear; D018106:CD28 Antigens; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D014612:Vaccines