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

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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

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Demyelinating Diseases
Virus Diseases
Spleen
Theilovirus
SCID Mice
Adoptive Transfer
T-Lymphocytes
Encephalitis Viruses
Satellite Viruses
RNA Viruses
Multiple Sclerosis
Spinal Cord
Cell Count
Viruses
Phenotype
Survival
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology

Cite this

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.

The Balance between Persistent Virus Infection and Immune Cells Determines Demyelination. / Rodriguez, Moses; Pavelko, Kevin D.; Njenga, M. Kariuki; Logan, William C.; Wettstein, Peter J.

In: Journal of Immunology, Vol. 157, No. 12, 15.12.1996, p. 5699-5709.

Research output: Contribution to journalArticle

Rodriguez, M, Pavelko, KD, Njenga, MK, Logan, WC & Wettstein, PJ 1996, 'The Balance between Persistent Virus Infection and Immune Cells Determines Demyelination', Journal of Immunology, vol. 157, no. 12, pp. 5699-5709.
Rodriguez M, Pavelko KD, Njenga MK, Logan WC, Wettstein PJ. The Balance between Persistent Virus Infection and Immune Cells Determines Demyelination. Journal of Immunology. 1996 Dec 15;157(12):5699-5709.
Rodriguez, Moses ; Pavelko, Kevin D. ; Njenga, M. Kariuki ; Logan, William C. ; Wettstein, Peter J. / The Balance between Persistent Virus Infection and Immune Cells Determines Demyelination. In: Journal of Immunology. 1996 ; Vol. 157, No. 12. pp. 5699-5709.
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