Cellular sources and targets of IFN-γ-mediated protection against viral demyelination and neurological deficits

Paul D. Murray, Dorian B. McGavern, Larry R. Pease, Moses Rodriguez

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

IFN-γ is an anti-viral and immunomodulatory cytokine critical for resistance to multiple pathogens. Using mice with targeted disruption of the gene for IFN-γ, we previously demonstrated that this cytokine is critical for resistance to viral persistence and demyelination in the Theiler's virus model of multiple sclerosis. During viral infections, IFN-γ is produced by natural killer (NK) cells, CD4+ and CD8+ T cells; however, the proportions of lymphocyte subsets responding to virus infection influences the contributions to IFN-γ-mediated protection. To determine the lymphocyte subsets that produce IFN-γ to maintain resistance, we used adoptive transfer strategies to generate mice with lymphocyte-specific deficiencies in IFN-γ-production. We demonstrate that IFN-γ production by both CD4+ and CD8+ T cell subsets is critical for resistance to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination and neurological disease, and that CD4+ T cells make a greater contribution to IFN-γ-mediated protection. To determine the cellular targets of IFN-γ-mediated responses, we used adoptive transfer studies and bone marrow chimerism to generate mice in which either hematopoietic or somatic cells lacked the ability to express IFN-γ receptor. We demonstrate that IFN-γ receptor must be present on central nervous system glia, but not bone marrow-derived lymphocytes, in order to maintain resistance to TMEV-induced demyelination.

Original languageEnglish (US)
Pages (from-to)606-615
Number of pages10
JournalEuropean Journal of Immunology
Volume32
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Glia
  • Multiple sclerosis
  • Neuroimmunology
  • Oligodendrocyte
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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