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Journal of Virology, June 2007, p. 6584-6593, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00008-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Differential Outcome of Tolerance Induction in Naive versus Activated Theiler's Virus Epitope-Specific CD8+ Cytotoxic T Cells{triangledown}

Meghann Teague Getts, Byung S. Kim, and Stephen D. Miller*

Department of Microbiology and Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, Illinois 60611

Received 2 January 2007/ Accepted 2 April 2007

Tolerance induced by the intravenous injection of peptide-pulsed, ethylene carbodiimide (ECDI)-fixed splenic antigen-presenting cells (Ag-SP) is a safe and effective method of inducing specific unresponsiveness in CD4+ T cells for the prevention and treatment of a variety of autoimmune diseases. We determined whether Ag-SP tolerance could also be used to tolerize CD8+ T cells. We show in the Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease model of multiple sclerosis that CD8+ T cells specific for both dominant and subdominant epitopes can be rendered tolerant. Interestingly, although virus clearance was delayed, lack of the virus-specific cytotoxic T-lymphocyte response did not result in the conversion of normally TMEV-resistant C57BL/6 mice to a susceptible phenotype. Importantly, we found that Ag-SP tolerance may not be a practical treatment for human diseases in which CD8+ T cells play a major role in pathogenesis, as tolerance induction in mice previously infected with TMEV led to a severe, often fatal reaction.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611. Phone: (312) 503-1449. Fax: (312) 503-1154. E-mail: s-d-miller{at}northwestern.edu

{triangledown} Published ahead of print on 11 April 2007.

Journal of Virology, June 2007, p. 6584-6593, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00008-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jin, Y.-H., Kang, B., Kim, B. S. (2009). Theiler's Virus Infection Induces a Predominant Pathogenic CD4+ T Cell Response to RNA Polymerase in Susceptible SJL/J Mice. J. Virol. 83: 10981-10992 [Abstract] [Full Text]  


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