TY - JOUR

T1 - Breakdown of blood-brain barrier function in the murine lymphocytic choriomeningitis virus infection mediated by virus-specific CD8+ T cells

AU - Andersen, I H

AU - Marker, O

AU - Thomsen, Allan Randrup

N1 - Keywords: Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, CD8; Antigens, Differentiation, T-Lymphocyte; Blood-Brain Barrier; Complement System Proteins; Epitopes; Immunocompetence; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Major Histocompatibility Complex; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Perfusion; T-Lymphocytes

PY - 1991

Y1 - 1991

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 1704015

VL - 31

SP - 155

EP - 163

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 2

ER -