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 transgenic mouse model to assess lymphocyte-astrocyte interactions. The major histocompatibility complex (MHC) class I molecule, Db, 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-Db fusion gene at the protein level. Functional antigen-presenting capacity was conferred by the Db transgene, as virus-infected primary astrocytes obtained from transgenic BALB/c mice (KdIdDdLd) expressing the Db molecule were lysed by Db-restricted anti-viral CTL.
Rall
G F
GF
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Mucke
L
L
Nerenberg
M
M
Oldstone
M B
MB
D000818:Animals; D001253:Astrocytes / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000235:genetics*; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics; D064532:Histocompatibility Antigen H-2D; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D005904:Glial Fibrillary Acidic Protein; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D012333:RNA, Messenger