Flügel A, Schwaiger F W, Neumann H, Medana I, Willem M, Wekerle H, Kreutzberg G W, Graeber M B
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, FRG.
Brain Pathol. 2000 Jul;10(3):353-64. doi: 10.1111/j.1750-3639.2000.tb00267.x.
Apoptosis of inflammatory cells plays a crucial role in the recovery from autoimmune CNS disease. However, the underlying mechanisms of apoptosis induction are as yet ill-defined. Here we report on the neuronal expression of FasL and its potential function in inducing T-cell apoptosis. Using a combination of facial nerve axotomy and passive transfer encephalomyelitis, the fate of CD4+ encephalitogenic T cells engineered to express the gene for green fluorescent protein was followed. FasL gene transcripts and FasL protein were detected in neurons by in sit-hybridization and immunohistochemistry. T cells infiltrating preferentially the injured brain parenchyma were found in the immediate vicinity of FasL expressing neurons and even inside their perikarya. In contrast to neurons, T cells rapidly underwent apoptosis. In co-cultures of hippocampal nerve cells and CD4 T lymphocytes, we confirmed expression of FasL in neurons and concomitant induction of T-cell death. Antibodies blocking neuronal FasL were shown to have a protective effect on T-cell survival. Thus, FasL expression by neurons in neuroinflammatory diseases may constitute a pivotal mechanism underlying apoptosis of encephalitogenic T cells.
炎症细胞凋亡在自身免疫性中枢神经系统疾病的恢复过程中起着关键作用。然而，诱导凋亡的潜在机制目前仍不清楚。在此，我们报道FasL在神经元中的表达及其在诱导T细胞凋亡中的潜在功能。采用面神经切断术和被动转移脑脊髓炎相结合的方法，追踪了经基因工程改造表达绿色荧光蛋白基因的CD4+致脑炎性T细胞的命运。通过原位杂交和免疫组织化学在神经元中检测到FasL基因转录本和FasL蛋白。优先浸润受损脑实质的T细胞位于表达FasL的神经元附近，甚至在其核周质内。与神经元不同，T细胞迅速发生凋亡。在海马神经细胞和CD4 T淋巴细胞的共培养中，我们证实了神经元中FasL的表达以及伴随的T细胞死亡诱导。阻断神经元FasL的抗体对T细胞存活具有保护作用。因此，神经炎症性疾病中神经元表达FasL可能是致脑炎性T细胞凋亡的关键机制。
