title: Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.
abstract: The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.
authors.affiliation: Department of Microbiology and Immunology, State University of New York-Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Nyland
authors.forename: M L
authors.initials: ML
authors.lastname: Stoll
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: F
authors.initials: F
authors.lastname: Feng
authors.forename: J
authors.initials: J
authors.lastname: Gavalchin
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization / Q000379:methods; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D007130:Immunoglobulin Idiotypes