Modulation of SLE induction in naive mice by specific T cells with suppressor activity to pathogenic anti-DNA idiotype.
T cells (CD8+) with specific suppressor activity against anti-dsDNA antibody (16/6 Id+) were generated in vitro. The cells were established from BALB/c-enriched T cells exposed in vitro to silica beads coated with the pathogenic anti-DNA idiotype, 16/6. The idiotype specificity of the suppressor cells was demonstrated by (a) specific induction of a decrease in proliferative response of T helper cell lines specific for the pathogenic idiotype (16/6 Id), when exposed to the idiotype, with no effect on T cell lines with other specificities, e.g., against human IgM or synthetic polypeptide. (b) Effectively suppressing in vitro antibody production of anti-16/6 antibody, employing 16/6-primed B cells and specific helper T cell line. The 16/6 Id-specific Ts cells were found to be MHC restricted. Weekly intravenous injections of 10(7) 16/6 Id-specific Ts cells given to BALB/c mice at different stages of experimental SLE disease prevented the clinical, serological, and pathological manifestations. This effect was characterized by decreased titers of autoantibodies (e.g., anti-DNA, anti-Sm antibodies) in the sera, by abolishment of the proteinuria, leukopenia, and the increased ESR, followed by decreased immunoglobulin deposition in the kidneys. Treating the mice with control IgM-specific T cells did not affect the above parameters. These studies demonstrate the ability to generate Ts cells specific for pathogenic idiotypes. The method might be employed therapeutically to modulate the course of autoimmune conditions.
Blank
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M
Steinmetz Research Unit of Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Ben-Bassat
M
M
Shoenfeld
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes