J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/06/2177/06 $2.00
Volume 185, Number 12, June 16, 1997 2177-2182

BRIEF DEFINITIVE REPORT:
Tumor Necrosis Factor  and Lymphotoxin  Are Not Required for Induction of Acute Experimental Autoimmune Encephalomyelitis

By Karl Frei,^* Hans-Pietro Eugster, Martin Bopst,^§ Cris S. Constantinescu, Ehud Lavi,^¶ and Adriano Fontana

From the ^* Department of Neurosurgery and  Section of Clinical Immunology, University Hospital Zürich, CH-8091 Zürich, Switzerland; ^§ Swiss Federal Institute of Technology, Institute of Toxicology, CH-8603 Schwerzenbach, Switzerland;  Department of Neurology and ^¶ Department of Pathology, Division of Neuropathology, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Immunization of mice with myelin components results in experimental autoimmune encephalomyelitis (EAE), which is mediated by myelin-specific CD4⁺ T cells and anti-myelin antibodies. Tumor necrosis factor  (TNF-) and lymphotoxin  (LT-) are thought to be involved in the events leading to inflammatory demyelination in the central nervous system. To ascertain this hypothesis 129 × C57BL/6 mice with an inactivation of the tnf and lta genes (129 × C57BL/6^/) and SJL/J mice derived from backcrosses of the above mentioned mutant mice (SJL^/) were immunized with mouse spinal cord homogenate (MSCH) or proteolipid protein. Both 129 × C57BL/6^/ mice and SJL^/ mice developed EAE. In SJL^/ mice immunized with MSCH, a very severe form of EAE with weight loss, paralysis of all four limbs, and lethal outcome was observed. The histologic hallmark was an intense perivascular and parenchymal infiltration with predominantly CD4⁺ T cells and some CD8⁺ T cells associated with demyelination in both brain and spinal cord. These results indicate that TNF- and LT- are not essential for the development of EAE.

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