Brain, Vol. 123, No. 10, 2005-2019,
October 2000
© 2000 Oxford University Press
TNFR1 signalling is critical for the development of demyelination and the limitation of T-cell responses during immune-mediated CNS disease
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1 Department of Molecular Genetics and Immunology, Hellenic Pasteur Institute, Athens, Greece, 2 Section of Clinical Immunology, Department of Internal Medicine and 3 Department of Neurosurgery, University Hospital Zurich, Switzerland and 4 Division of Neuroimmunology, Brain Research Institute, University of Vienna, Austria
Correspondence to:
Adriano Fontana, Section of Clinical Immunology, Department of Internal Medicine, University Hospital Zurich, Häldeliweg 4, CH-8044 Zurich, Switzerland E-mail: immfoa{at}usz.unizh.ch
In this review we summarize the essential findings about the function of tumour necrosis factor (TNF) and its cognate receptors TNFR1 and TNFR2, and lymphotoxin 
(LT-) ligands in immune-mediated CNS inflammation and demyelination. The advent of homologous recombination technology in rodents provides a new method which has been used during the last 5 years and has led to insights into the pathophysiology of experimental autoimmune encephalomyelitis (EAE) in an unprecedented way. Studies with knockout mice in which genes of the TNF ligand/receptor superfamily are not expressed and studies with transgenic mice overexpressing TNF and TNFR reveal the critical role of the TNFR1 signalling pathway in the control of CNS demyelination and inflammation. These studies provide novel findings and at the same time shed light on the complex pathophysiology of EAE. Together, these findings may contribute to better understanding of EAE and open new avenues in experimental therapies for multiple sclerosis.
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