Andersen I H, Marker O, Thomsen A R
Institute of Medical Microbiology, University of Copenhagen, Denmark.
J Neuroimmunol. 1991 Feb;31(2):155-63. doi: 10.1016/0165-5728(91)90021-x.
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.
脑内接种淋巴细胞性脉络丛脑膜炎病毒（LCMV）通常会导致致命的T细胞介导的脑膜炎。在先前的一项研究中，我们已经证明在这种情况下血脑屏障（BBB）受损。现在，我们使用半定量放射成像和低分子示踪剂2-氨基-[1-¹⁴C]异丁酸，证明在脑内感染的T细胞缺陷型裸鼠（nu/nu）中血脑屏障未受损，但在杂合子同窝小鼠中存在严重功能障碍。采用转移实验来表征和比较参与诱导血脑屏障功能障碍和致命疾病的细胞亚群。结果表明，Thy-1⁺、CD8⁺ I类限制性T细胞对于血脑屏障通透性增加以及死亡率而言是必需的。此外，II类限制性CD4⁺细胞的耗竭显著削弱了细胞转移的两种效应。这些结果支持了病毒特异性T细胞活性、血脑屏障功能障碍和致命疾病之间存在因果关系的观点。此外，数据表明辅助性T细胞增强了LCMV特异性CD8⁺效应细胞的反应。
