Reduction of lupus nephritis in MRL/lpr mice by a bacterial superantigen treatment.
The effects of biweekly intravenous injections of Staphylococcus Enterotoxin B (SEB) into autoimmune MRL-lpr/lpr (MRL/lpr) mice were investigated. Rather than causing the expansion of V beta 8+ T cells, SEB administration resulted in the reduction V beta 8+, CD4-CD8- "double-negative" (DN) T cells. This was shown by FACS analysis as this putative pathogenic population was diminished in both spleen and lymph node. The symptoms of systemic lupus erythematosus (SLE) in MRL/lpr, which include high titers of anti-DNA antibodies and circulating immune complexes and proteinuria, were reduced in SEB-treated mice in a dose-dependent manner. The clinical parameters of SLE in MRL/lpr, which include lymph node hyperplasia and necrotic vasculitis, were suppressed in 50-micrograms SEB-treated mice. T cells bearing V beta 6 T cell receptor, which does not interact with SEB, were not reduced with SEB administration. Thus, disease suppression was associated with a specific reduction in the number of V beta 8+, DN T cells. These results implicate a possible therapeutic role of superantigen-based immunotherapy in V beta-restricted, T cell-dominated clinical syndromes.
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Division of Neurobiology and Molecular Immunology, Samuel S. Lunenfeld Research Instiute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Siminovitch
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Ochi
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D000818:Animals; D000906:Antibodies / Q000032:analysis; D000936:Antigen-Antibody Complex / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004247:DNA / Q000276:immunology; D004768:Enterotoxins / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000517:prevention & control*; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D011507:Proteinuria / Q000517:prevention & control; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013211:Staphylococcus aureus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D000936:Antigen-Antibody Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D004768:Enterotoxins; D011948:Receptors, Antigen, T-Cell; C031818:enterotoxin B, staphylococcal; D004247:DNA