Elevated interferon gamma expression in the central nervous system of tumour necrosis factor receptor 1-deficient mice with experimental autoimmune encephalomyelitis

    loading  Checking for direct PDF access through Ovid

Abstract

Summary

Inflammation in the central nervous system (CNS) can be studied in experimental autoimmune encephalomyelitis (EAE). The proinflammatory cytokines interferon-gamma (IFN-γ) and tumour necrosis factor (TNF) are implicated in EAE pathogenesis. Signals through the type 1 TNF receptor (TNFR1) are required for severe EAE to develop, whereas deficiency in IFN-γ or its receptor result in more severe EAE. We investigated IFN-γ expression in TNFR1-deficient (TNFR1–/–) mice. We describe here that there were more IFN-γ-secreting T cells present in the CNS of TNFR1–/– mice during EAE compared to wild-type (WT) mice, despite that clinical symptoms were mild, with delayed onset. There was greater expression of IL-12/23p40 by antigen-presenting cells in these mice, and in vitro, TNFR1–/– antigen-presenting cells induced greater secretion of IFN-γ but not interleukin (IL)-17 when cultured with primed T cells than did WT antigen presenting cells. TNFR1–/– mice with EAE had significantly higher expression of CXCL10 mRNA (but not CCL5 mRNA) in the CNS compared to WT mice with EAE. These data demonstrate that IFN-γ expression is enhanced in the CNS of TNFR1–/– mice with EAE and suggest that IFN-γ levels do not necessarily correlate with EAE severity.

Related Topics

    loading  Loading Related Articles