Neuronal FasL induces cell death of encephalitogenic T lymphocytes

Brain Pathol. 2000 Jul;10(3):353-64. doi: 10.1111/j.1750-3639.2000.tb00267.x.

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 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.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Apoptosis
  • Brain / pathology
  • Brain / physiopathology
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Coculture Techniques
  • Encephalomyelitis / etiology*
  • Encephalomyelitis / pathology
  • Facial Nerve / cytology
  • Facial Nerve / metabolism
  • Fas Ligand Protein
  • Gene Expression
  • Green Fluorescent Proteins
  • Hippocampus / cytology
  • Immunohistochemistry
  • In Situ Hybridization
  • Indicators and Reagents
  • Luminescent Proteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology*
  • Motor Neurons / metabolism
  • Neurons / metabolism*
  • Neurons / physiology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew

Substances

  • Antibodies
  • Fas Ligand Protein
  • Faslg protein, rat
  • Indicators and Reagents
  • Luminescent Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • Green Fluorescent Proteins