Severity of symptoms and demyelination in MOG-induced EAE depends on TNFR1.

The individual role of tumor necrosis factor receptor 1 (TNFR1) and TNFR2 signaling in experimental autoimmune encephalomeylitis (EAE) was investigated using mice lacking TNFR1 (TNFR1-/-), TNFR2 (TNFR2-/-) as well as double receptor (TNFR1/2-/-) and double ligand (TNF/LT alpha-/-) knockout mice. In wild-type (wt) mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 the clinical course is characterized by an acute disease onset with peak disease scores and a consecutive chronic phase lasting up to 60 days. Compared to control mice, TNF/LT alpha-deficient mice showed a significant delay in disease onset and a remarkable reduction in demyelination which was, however, associated with increased inflammation. In TNFR1-/- and TNFR1/2-/- mice, the disease course was comparable to TNF/LT alpha-deficient mice but rather monophasic and less severe at late time points. Likewise only minimal spinal cord demyelination became apparent. In contrast, the course of EAE in TNFR2-/- mice was severe and associated with remarkable demyelination. Taken together these findings define TNFR1 as crucial mediator in MOG-induced EAE and suggest a protective role for TNFR2 signaling in the clinical course of EAE.