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. 2006 Apr 5;10(3):353–364. doi: 10.1111/j.1750-3639.2000.tb00267.x

Neuronal FasL Induces Cell Death of Encephalitogenic T Lymphocytes

A Flügel 1, F W Schwaiger 2, H Neumann 1, I Medana 1, M Willem 3, H Wekerle 1, GW Kreutzberg 2, MB Graeber 2,4,✉
PMCID: PMC8098261  PMID: 10885654

Abstract

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 situ‐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.

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