IMMUNIZATION-INDUCED INFLAMMATORY INFILTRATION OF THE CENTRAL-NERVOUS-SYSTEM IN TRANSGENIC MICE EXPRESSING A MICROBIAL ANTIGEN IN ASTROCYTES

Transgenic mice expressing a defined microbial antigen from central ne rvous system (CNS) cell type-specific promoters can be utilized to inv estigate the consequences of induction of peripheral immune responses to foreign antigens produced by different CNS cell types. Immunization of mice expressing beta-galactosidase (beta-gal) in astrocytes with t his protein resulted in antigen-dependent infiltration of the CNS by m ononuclear cells, principally CD4(+) T lymphocytes and monocyte/macrop hages. The perivascular and intraparenchymal infiltrates, which were l ocated predominantly in the hippocampal formation and cerebellum, the areas of highest beta-gal expression, were associated with astrocytosi s, microgliosis, and a generalized increase in blood-brain barrier per meability. The resemblance of these pathological changes to aspects of human immune inflammatory CNS disorders, e.g. multiple sclerosis, sug gests that an initiating step in the process by which such complex dis eases are produced could be the induction of peripheral immune respons es to antigens expressed in astrocytes.