title: TNF accelerates the onset but does not alter the incidence and severity of myelin basic protein-induced experimental autoimmune encephalomyelitis.
abstract: Experimental autoimmune encephalomyelitis (EAE) induction in TNF gene-targeted mice has resulted in conflicting reports in part due to the strong association of TNF with the MHC locus. To define the participation of TNF in EAE development, we back-crossed TNF-deficient mice (H-2b) into the SJL/J strain and directly compared them to H-2b congenic SJL or inbred SJL/J mice. Induction of EAE with myelin basic protein (MBP) revealed that H-2b congenic SJL mice are fully susceptible, indicating that the H-2b haplotype does not affect disease susceptibility. Using H-2b congenic SJL mice we show here that TNF deficiency modifies the normal course of EAE by considerably delaying the onset for approximately 5 days, suggesting that TNF is required for the normal initiation of MBP-induced EAE. However, TNF-deficient mice eventually developed severe EAE with perivascular inflammation and primary demyelination similar to wild-type controls, indicating that TNF is not essential during these processes. Taken together, these results indicate that although TNF is not required for the progression of MBP-induced EAE, it contributes positively by advancing the onset of disease.
authors: Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece.
authors: G
authors: G
authors: Kassiotis
authors: M
authors: M
authors: Pasparakis
authors: G
authors: G
authors: Kollias
authors: L
authors: L
authors: Probert
mesh_terms: D000818:Animals; D002490:Central Nervous System; D003711:Demyelinating Diseases; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha