Flow cytometric and functional analyses of central nervous system-infiltrating cells in SJL/J mice with Theiler's virus-induced demyelinating disease: Evidence for a CD4+ T cell-mediated pathology

Jonathan G. Pope, William J. Karpus, Carol Vanderlugt, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Theiler's murine encephalomyelitis viruses (TMEVs) are endemic enteric pathogens of mice that cause immune-mediated, chronic, progressive, central nervous system (CNS) demyelinating disease in susceptible strains. Analysis of T cell phenotype and functional state from TMEV-infected SJL/J mice by flow cytometry reveals that 13.5 to 25% of the CD4+ T cells in the CNS express high affinity IL-2R, a marker of recent T cell activation, whereas splenic levels of CD4+IL-2R+ T cells generally range between 2 and 8.5%. In contrast, very few CD8+ T cells (<1-2%) from either site express IL-2R. From days 20 to 119 postinfection, the percentage of CD4+IL-2R+ T cells increases gradually in the CNS, but varies little in the spleen. CD4+ T cells isolated from the spinal cord of infected mice proliferate in vitro in response to viral Ag. Similar T cell phenotypes were found in experimental autoimmune encephalomyelitis, an established model of CD4+ T cell-mediated demyelination. In addition, most CD4+ and CD8+ T cells in CNS isolates from TMEV-infected mice are CD44+, indicating that prior activation may be required to traffic through and/or be retained in the CNS. Finally, TCR Vβ region usage as well as IL-2R expression by individual Vβ region subsets are heterogeneous in both the CNS and spleen. These results are consistent with a model in which a polyclonal population of TMEV-specific, CD4+ Th1 cells plays a major effector role in the demyelinating process.

Original languageEnglish (US)
Pages (from-to)4050-4058
Number of pages9
JournalJournal of Immunology
Volume156
Issue number10
StatePublished - May 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Flow cytometric and functional analyses of central nervous system-infiltrating cells in SJL/J mice with Theiler's virus-induced demyelinating disease: Evidence for a CD4<sup>+</sup> T cell-mediated pathology'. Together they form a unique fingerprint.

Cite this