The Balance between Persistent Virus Infection and Immune Cells Determines Demyelination

Moses Rodriguez, Kevin D. Pavelko, M. Kariuki Njenga, William C. Logan, Peter J. Wettstein

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

We addressed the contributions of persistent virus infection and immune cells to the pathogenesis of Theiler's virus-induced demyelination, a model for human multiple sclerosis. We developed a model involving the transfer of spleen cells into immunodeficient C.B-17-scid (SCID) mice, which normally die of overwhelming virus encephalitis without demyelination when infected with Theiler's virus. Adoptive transfer of nonimmune spleen cells from BALB/c mice into SCID mice resulted in the survival of all mice. However, these mice developed extensive demyelination and virus Ag/RNA persistence in the spinal cord white matter. The most demyelination was observed when mice received an intermediate number of spleen cells (1.8-7.5 × 106), whereas too few cells (0.5 × 106) did not ameliorate the SCID phenotype, and too many cells (30 × 106) resulted in almost complete viral clearance with minimal demyelination. Adoptive transfer of spleen cells depleted of either CD4+ or CD8+ T cells produced vacuolar demyelination associated with virus persistence. In contrast, reconstitution with both CD4+ and CD8+ T cells produced less severe demyelination and partial clearance of virus. These experiments support the hypothesis that demyelination is the result of a balance between persistent virus infection and immune injury mediated by either CD4+ or CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)5699-5709
Number of pages11
JournalJournal of Immunology
Volume157
Issue number12
StatePublished - Dec 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rodriguez, M., Pavelko, K. D., Njenga, M. K., Logan, W. C., & Wettstein, P. J. (1996). The Balance between Persistent Virus Infection and Immune Cells Determines Demyelination. Journal of Immunology, 157(12), 5699-5709.