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

• Published in: European journal of immunology Vol. 29; no. 2; pp. 626 - 632
• Main Authors: Eugster, Hans‐Pietro, Frei, Karl, Bachmann, Rosilla, Bluethmann, Horst, Lassmann, Hans, Fontana, Adriano
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.02.1999
• Subjects: Animals; Autoimmunity; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - physiopathology; Inflammation; Knockout; Mice; Mice, Knockout; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein - immunology; Myelin-Oligodendrocyte Glycoprotein; Neuroimmunology; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - immunology; Tumor necrosis factor
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199902)29:02<626::AID-IMMU626>3.0.CO;2-A

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 / LTα− / −) 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 / LTα‐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 / LTα‐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.