Amelioration of lpr^<cg>-induced autoimmune diseases with Vbeta8.2-specific viral superantigen and its application to gene therapy in mice

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MRL-lpr^<cg>/lpr^<cg> (MRL-lpr^<cg>) mice were established by introducing lpr^<cg> gene into MRL mice by 12 generations of backcross. Their newborns were forster-nursed on FM mothers to establish MRL-lpr^<cg>fFM carrying mouse mammary tumor virus (MMTV) encoding Vbeta8.2-specific superantigen (SAg). One-year survey revealed that MRL-lpr^<cg>fFM mice survived longer and had lower levels of proteinuria than MRL-lpr^<cg>. Autopsy at 3 and 5 months of age demonstrated less severe lymphoproliferative disease in MRL-lpr^<cg>fFM.Histological and immunofluorescent examinations indicated that the incidence of clinical glomerulonephritis was clearly lower and the amount of adhered immune complex was smaller in MRL-lpr^<cg>fFM than in MRL-lpr^<cg> mice. Serological analyzes revealed that the total IgG level and anti-DNA antibody levels of IgG class and IgG2a and IgG3 subclasses were lower in MRL-lpr^<cg>fFM mice. Vbeta8.2+ cells were almost completely depleted in CD4+, CD8+ and CD4-8- T cell populations in MRL-lpr^<cg>fFM mice. These results evidenced that MMTV (FM) SAg ameliorated autoimmune diseases by suppressing autoantibody production through deletion of Vbeta8.2+ cells and support the application of viral SAg to gene therapy.