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

J Neuroimmunol. 1994 Jun;52(1):61-8. doi: 10.1016/0165-5728(94)90163-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / immunology*
  • Base Sequence
  • Female
  • Glial Fibrillary Acidic Protein / analysis
  • Glial Fibrillary Acidic Protein / genetics*
  • H-2 Antigens / biosynthesis*
  • H-2 Antigens / genetics
  • Histocompatibility Antigen H-2D
  • Lymphocytic choriomeningitis virus / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • RNA, Messenger / analysis
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Glial Fibrillary Acidic Protein
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • RNA, Messenger