Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG35-55-induced experimental autoimmune encephalomyelitis

Graig C. Suvannavejh, Hae Ock Lee, Josette Padilla, Mauro C. Dal Canto, Terrance A. Barrett, Stephen D. Miller

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

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 languageEnglish
Pages (from-to)24-33
Number of pages10
JournalCellular Immunology
Volume205
Issue number1
DOIs
StatePublished - 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.

Keywords

  • Autoimmunity
  • CNS
  • EAE
  • Inflammation
  • MS
  • Regulation
  • TNF
  • TNF receptor
  • p55
  • p75

ASJC Scopus subject areas

  • Immunology

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