TNF accelerates the onset but does not alter the incidence and severity ofmyelin basic protein-induced experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) induction in TNF gene-targe ted mice has resulted in conflicting reports in part due to the strong asso ciation of TNF with the MHC locus. To define the participation of TNF in EA E development, we back-crossed TNF-deficient mice (H-2b) into the SJL/J str ain and directly compared them to H-2b congenic SJL or inbred SJL/J mice. I nduction of EAE with myelin basic protein (MBP) revealed that H-2b congenic SJL mice are fully susceptible, indicating that the H-2b haplotype does no t affect disease susceptibility. Using H-2b congenic SJL mice we show here that TNF deficiency modifies the normal course of EAE by considerably delay ing the onset for approximately 5 days, suggesting that TNF is required for the normal initiation of MBP-induced EAE. However, TNF-deficient mice even tually developed severe EAE with perivascular inflammation and primary demy elination similar to wild-type controls, indicating that TNF is not essenti al during these processes. Taken together, these results indicate that alth ough TNF is not required for the progression of MBP-induced EAE, it contrib utes positively by advancing the onset of disease.