Neuronal FasL induces cell death of encephalitogenic T lymphocytes.
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.
Flügel
A
A
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, FRG.
Schwaiger
F W
FW
Neumann
H
H
Medana
I
I
Willem
M
M
Wekerle
H
H
Kreutzberg
G W
GW
Graeber
M B
MB
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D004679:Encephalomyelitis / Q000209:etiology* / Q000473:pathology; D005154:Facial Nerve / Q000166:cytology / Q000378:metabolism; D053222:Fas Ligand Protein; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007202:Indicators and Reagents; D008164:Luminescent Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D009046:Motor Neurons / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins