Abstract
To clarify the role of tumor necrosis factor (TNF) in the inflammatory aspects of autoimmunity vs its potential role in the apoptotic elimination of auto-reactive effector cells, we assessed the roles of the p55 (TNFR1/Tnfrsf1a/CD120a) and p75 (TNFR2/ Tnfrsf1b/CD120b) TNF receptors in the pathogenesis of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). TNFR p55/p75(-/-) double knockout mice were completely resistant to clinical disease. TNFR p55(-/-) single knockout mice were also totally resistant to EAE, exhibiting reduced MOG35-55-specific proliferative responses and Th1 cytokine production, despite displaying equivalent DTH responses. Importantly, IL-5 was significantly increased in p55(-/-) mice. In contrast, p75(-/-) knockout mice exhibited exacerbated EAE, enhanced Th1 cytokine production, and enhanced CD4+ and F4/80+ CNS infiltration. Thus, p55/TNFR1 is required for the initiation of pathologic disease, whereas p75/TNFR2 may be important in regulating the immune response. These results have important implications for therapies targeting p55 and p75 receptors for treating autoimmune diseases. (C) 2000 Academic Press.
Original language | English |
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Pages (from-to) | 24-33 |
Number of pages | 10 |
Journal | Cellular Immunology |
Volume | 205 |
Issue number | 1 |
DOIs | |
State | Published - Oct 10 2000 |
Bibliographical note
Funding Information:This work was supported by U.S. Public Health Service/National Institutes of Health Grants NS26543, NS30871, and NS13011 and by National Multiple Sclerosis Society Grant RG2893.
Funding
Funders | Funder number |
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National Institute of Neurological Disorders and Stroke | R01NS030871 |
Keywords
- Autoimmunity
- CNS
- EAE
- Inflammation
- MS
- Regulation
- TNF
- TNF receptor
- p55
- p75
ASJC Scopus subject areas
- Immunology