A transgenic mouse model to assess the interaction of cytotoxic T lymphocytes with virally infected, class I MHC-expressing astrocytes

Rall, Glenn F.; Mucke, Lennart; Nerenberg, Michael; Oldstone, Michael B.A.

Astrocytes provide crucial support for neurons and their impairment by viruses or their interactions with anti-viral or autoimmune responses could contribute to neurological disease. We have developed a transgenic mouse model to assess lymphocyte-astrocyte interactions. The major histocompatibility complex (MHC) class I molecule, D(b), was expressed in astrocytes under the transcriptional control of regulatory sequences from the glial fibrillary acidic protein (GFAP) gene. Baseline cerebral MHC class I mRNA levels from transgenic mice were elevated over those of non-transgenic controls, and a prominent increase in cerebral MHC class I expression occurred following focal, injury-induced astroglial activation within transgenic brains but not in non-transgenic controls. FACS analysis of explant astrocyte cultures from established transgenic lines demonstrated astroglial expression of the GFAP-D(b) fusion gene at the protein level. Functional antigen-presenting capacity was conferred by the D(b) transgene, as virus-infected primary astrocytes obtained from transgenic BALB/c mice (K(d)I(d)D(d)L(d)) expressing the D(b) molecule were lysed by D(b)-restricted anti-viral CTL.