Protection against renal disease in (NZB X NZW)F1 lupus-prone mice after somatic B cell gene vaccination with anti-DNA immunoglobulin consensus peptide

Francesca Ferrera, Bevra H. Hahn, Marta Rizzi, Marissa Anderson, John FitzGerald, Enrico Millo, Francesco Indiveri, Fu Dong Shi, Gilberto Filaci, Antonio La Cava

Research output: Contribution to journalArticlepeer-review

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)F1 (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 β-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. Conclusion. 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.

Original languageEnglish
Pages (from-to)1945-1953
Number of pages9
JournalArthritis and Rheumatism
Volume56
Issue number6
DOIs
Publication statusPublished - Jun 2007

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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