TUMOR-NECROSIS-FACTOR-ALPHA AND LYMPHOTOXIN-ALPHA ARE NOT REQUIRED FOR INDUCTION OF ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Immunization of mice with myelin components results in experimental au toimmune encephalomyelitis (EAE), which is mediated by myelin-specific CD4(+) T cells and anti-myelin antibodies. Tumor necrosis factor alph a (TNF-alpha) and lymphotoxin alpha (LT-alpha) are thought to be invol ved in the events leading to inflammatory demyelination in the central nervous system. To ascertain this hypothesis 129 x C57BL/6 mice with an inactivation of the tnf and Ita genes (129 x C57BL/6(-/-)) and SJL/ J mice derived h-om backcrosses of the above mentioned mutant mice (SJ L(-/-)) were immunized with mouse spinal cord homogenate (MSCH) or pro teolipid protein. Both 129 x C57BL/6(-/-) mice and SJL(-/-) mice devel oped 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 CD 8(+) T cells associated with demyelination in both brain and spinal co rd. These results indicate that TNF-alpha and LT-alpha are not essenti al for the development of EAE.