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 language | English (US) |
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Pages (from-to) | 27-37 |
Number of pages | 11 |
Journal | Journal of Neuroimmunology |
Volume | 226 |
Issue number | 1-2 |
DOIs | |
State | Published - Sep 2010 |
Funding
This work was supported by National Institutes of Health grants RO1 NS28752 and RO1 NS33008 , and by a grant ( RG 4001A6 ) from the National Multiple Sclerosis Society .
Keywords
- CNS infiltration
- Co-stimulatory molecules
- T cell responses
- TMEV
- Type I IFNs
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
- Immunology and Allergy
- Immunology