A TRANSGENIC MOUSE MODEL TO ASSESS THE INTERACTION OF CYTOTOXIC T-LYMPHOCYTES WITH VIRALLY INFECTED, CLASS-I MHC-EXPRESSING ASTROCYTES

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 transge nic 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 sequenc es from the glial fibrillary acidic protein (GFAP) gene. Baseline cere bral MHC class I mRNA levels from transgenic mice were elevated over t hose of non-transgenic controls, and a prominent increase in cerebral MHC class I expression occurred following focal, injury-induced astrog lial activation within transgenic brains but not in non-transgenic con trols. FACS analysis of explant astrocyte cultures from established tr ansgenic lines demonstrated astroglial expression of the GFAP-D-b fusi on gene at the protein level. Functional antigen-presenting capacity w as conferred by the D-b transgene, as virus-infected primary astrocyte s obtained from transgenic BALB/c mice (K(d)I(d)D(d)L(d)) expressing t he D-b molecule were lysed by D-b-restricted anti-viral CTL.