Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease

Evans, Claire F.; Horwitz, Marc S.; Hobbs, Monte V.; Oldstone, Michael B.A.

Characterization of the Immune Response to LCMV in Transgenic Mice. This model requires the transgenic mice to mount an immune response against the transgene, which is a self-protein. Therefore, the first question addressed was whether the transgenic mice were immunologically responsive to the transgene (self) products. The ability of the MBP-LCMV transgenic mice to generate both anti-viral (self) CTL and antibodies was assessed. CTL responses of the transgenic mice were measured in 51 Cr release assays using splenic lymphocytes harvested 7 d after infection with LCMV. Transgenic and nontransgenic mice from all four transgenic MBP-NP and -GP lines were able to lyse MHC-matched target cells infected with LCMV (Table 1 ). In addition, BALB clone 7 (H-2 d ) target cells infected with a recombinant VV expressing the NP from LCMV (VV-NP) were lysed by lymphocytes from MBP-NP transgenic positive and negative mice. Likewise, MC57 (H-2 b ) target cells infected with a recombinant vaccinia virus expressing the GP from LCMV (VV-GP) were effectively lysed by lymphocytes from MBP-GP transgenic positive and negative mice. The ability of transgenic mice to mount anti-LCMV antibody responses was evaluated using an ELISA assay with gradient-purified LCMV. At 2 mo after infection with LCMV, MBP-NP and -GP transgenic positive and negative mice showed good antibody responses (antibody titers Ͼ 10 5 ; data not shown). Thus, the transgenic positive mice generated LCMV-specific humoral and cellular immune responses equivalent to transgenic negative mice, indicating they were able to mount immune responses to the viral self-proteins expressed as transgenes.