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.
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.
Ferrera
Francesca
F
David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Hahn
Bevra H
BH
Rizzi
Marta
M
Anderson
Marissa
M
Fitzgerald
John
J
Millo
Enrico
E
Indiveri
Francesco
F
Shi
Fu-Dong
FD
Filaci
Gilberto
G
La Cava
Antonio
A
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*
D000974:Antibodies, Antinuclear; D018106:CD28 Antigens; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D014612:Vaccines