Alleviation of Renal Disease and Lymphadenopathy in MRL- Fas lprcg /Fas lprcg (MRL- lpr cg ) Mice Neonatally Infected with Mouse Mammary Tumor Virus Encoding Superantigen Strongly Reactive with TCR Vβ8.2 Element

Abstract

Mouse mammary tumor virus transmitted by FM mice (FM-MMTV) encodes a superantigen (SAg) characterized by strong reactivity with TCR Vβ8.2 element and broad spectrum of Vβ reactivity. To investigate what effects the expression in vivo of FM-MMTV SAg exhibits on the course of the disease in a lupus-prone model, MRL/MpJ-Fas^lprcg/Fas^lprcg (MRL-lpr^cg ) mice, neonatally FM-MMTV-infected MRL-lpr ^cg(MMTV) and uninfected MRL-lpr ^cg mice were compared for various disease parameters. In MRL-lpr^cg (MMTV), survival was significantly prolonged, glomerulonephritis, proteinuria, and lymphadenopathy were clearly ameliorated, and the production of serum immunoglobulin G (IgG), complement-activating IgG_2a, and cryogenic IgG3 autoantibodies, which are thought to be pathogenic to kidneys, and circulating immune complexes (IC), and glomerular IC deposition were significantly suppressed. FM-MMTV infection deleted Vβ8.2⁺ cells by about 90% and Vβ14⁺ cells less efficiently in all of the CD4⁺, CD8⁺, and B220⁺ CD4^- CD8^- or double-negative(DN) T-cell populations, and Vβ8.1⁺ cells in the CD4⁺ population but not in the others. Similar deletion profiles of CD8⁺ and DN T cells support that DN T cells are derived from the CD8 lineage. The results imply that the specific regulation of the immune system with viral SAg has a potential for development of an attractive immunomodulatory therapy of autoimmune diseases.