The role of cellular immune response in Theiler's virus-induced central nervous system demyelination

M. Kariuki Njenga, Cristina Marques, Moses Rodriguez

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Theiler's murine encephalomyelitis virus (TMEV) persists in spinal cord white matter of susceptible mice (e.g., SJL/J), resulting in chronic inflammation and demyelination. Reconstitution of severe combined immunodeficient (SCID) mice with CD4+ T- or CD8+ T-lymphocytes results in extensive TMEV-induced demyelination, and depletion of CD8+ T-lymphocytes in the early or late phase of the disease decreases the extent of demyelination, indicating that the cellular immune response against the virus plays a key role in myelin destruction. In susceptible mice, the demyelinated lesions are characterized by infiltration of a large numbers of B- and T-lymphocytes; whereas in mice resistant to TMEV-induced demyelination (e.g., C57BL/6), virus clearance requires infiltration of between 2.9×105 and 5.7×105 CD8+ T-lymphocytes and between 3.4×105 and 6.1×105 CD4+ T-lymphocytes per mouse in the brain 5-9 days post infection. Transgenic expression of capsid proteins of TMEV abrogates resistance in C56BL/6 mice, rendering the mice susceptible to TMEV persistence and demyelination. Comparison of the kinetics of virus replication and B- and T-lymphocyte infiltration in mice lacking key adhesion molecules (L-selectin (L-sel-/-), P-selectin (P-sel-/-), intracellular adhesion molecule-1 (ICAM-1-/-), or leukocyte function-associated antigen-1 (LFA-1-/-)) demonstrates a role for individual adhesion molecules in recruitment of immune cells into central nervous system (CNS), but the role is not significant to prevent eventual virus clearance.

Original languageEnglish (US)
Pages (from-to)73-77
Number of pages5
JournalJournal of neuroimmunology
Volume147
Issue number1-2
DOIs
StatePublished - Feb 2004

Keywords

  • Adhesion molecules
  • Cellular immune response
  • Demyelination
  • Theiler's syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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