Type I interferon signals control Theiler's virus infection site, cellular infiltration and T cell stimulation in the CNS

Young Hee Jin, Wanqiu Hou, Seung Jae Kim, Alyson C. Fuller, Bongsu Kang, Gwen Goings, Stephen D. Miller, Byung S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Theiler's murine encephalomyelitis virus (TMEV) establishes a persistent infection in the central nervous system (CNS). To examine the role of type I interferon (IFN-I)-mediated signals in TMEV infection, mice lacking a subunit of the type I IFN receptor (IFN-IR KO mice) were utilized. In contrast to wild type mice, IFN-IR KO mice developed rapid fatal encephalitis accompanied with greater viral load and infiltration of immune cells to the CNS. The proportion of virus-specific CD4+ and CD8+ T cell responses in the CNS was significantly lower in IFN-IR KO mice during the early stage of infection. Levels of IFN-γ and IL-17 produced by isolated primed CD4+ T cells in response to DCs from TMEV-infected IFN-IR KO mice were also lower than those stimulated by DCs from TMEV-infected wild type control mice. The less efficient stimulation of virus-specific T cells by virus-infected antigen-presenting cells is attributable in part to the low level expression of activation markers on TMEV-infected cells from IFN-IR KO mice. However, due to high levels of cellular infiltration and viral loads in the CNS, the overall numbers of virus-specific T cells are higher in IFN-IR KO mice during the later stage of viral infection. These results suggest that IFN-I-mediated signals play important roles in controlling cellular infiltration to the CNS and shaping local T cell immune responses.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalJournal of Neuroimmunology
Volume226
Issue number1-2
DOIs
StatePublished - Sep 2010

Keywords

  • CNS infiltration
  • Co-stimulatory molecules
  • T cell responses
  • TMEV
  • Type I IFNs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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