Breakdown of blood-brain barrier function in the murine lymphocytic choriomeningitis virus infection mediated by virus-specific CD8+ T cells.
Intracerebral inoculation of lymphocytic choriomeningitis virus (LCMV) generally results in a fatal T cell-mediated meningitis. In a previous study we have demonstrated a compromised blood-brain barrier (BBB) under such conditions. Using semi-quantitative radiography and the low molecular tracer 2-amino-[1-14C]isobutyric acid we now demonstrate an uncompromised BBB in i.c. infected T cell-deficient nu/nu mice, but serious dysfunction in heterozygous littermates. Transfer experiments were used to characterize and compare the cell subset(s) involved in inducing BBB dysfunction and fatal disease. It was demonstrated that Thy-1+, CD8+ class I-restricted T cells were mandatory for the increase in BBB permeability as well as for mortality. In addition, depletion of class II-restricted CD4+ cells significantly weakened both effects of cell transfer. These results support the idea of a causal relationship between virus-specific T cell activity, BBB dysfunction, and fatal disease. Furthermore, the data indicate that T helper cells augment the response of LCMV-specific CD8+ effector cells.
Andersen
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IH
Institute of Medical Microbiology, University of Copenhagen, Denmark.
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Thomsen
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D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001812:Blood-Brain Barrier; D016827:CD8 Antigens; D003165:Complement System Proteins; D000939:Epitopes; D007121:Immunocompetence; D008216:Lymphocytic Choriomeningitis / Q000503:physiopathology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010477:Perfusion; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D000939:Epitopes; D003165:Complement System Proteins