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Journal of Virology, March 2005, p. 3370-3381, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3370-3381.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Increased Epitope-Specific CD8+ T Cells Prevent Murine Coronavirus Spread to the Spinal Cord and Subsequent Demyelination

Katherine C. MacNamara,1 Ming Ming Chua,1 Peter T. Nelson,2 Hao Shen,1 and Susan R. Weiss1*

Department of Microbiology,1 Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania2

Received 17 August 2004/ Accepted 2 November 2004

CD8+ T cells are important for clearance of neurotropic mouse hepatitis virus (MHV) strain A59, although their possible role in A59-induced demyelination is not well understood. We developed an adoptive-transfer model to more clearly elucidate the role of virus-specific CD8+ T cells during the acute and chronic phases of infection with A59 that is described as follows. C57BL/6 mice were infected with a recombinant A59 virus expressing the gp33 epitope, an H-2Db-restricted CD8+ T-cell epitope encoded in the glycoprotein of lymphocytic choriomeningitis virus, as a fusion with the enhanced green fluorescent protein (RA59-gfp/gp33). P14 splenocytes (transgenic for a T-cell receptor specific for the gp33 epitope) were transferred at different times pre- and postinfection (p.i.). Adoptive transfer of P14 splenocytes 1 day prior to infection with RA59-gfp/gp33, but not control virus lacking the gp33 epitope, RA59-gfp, reduced weight loss and viral replication and spread in the brain and to the spinal cord. Furthermore, demyelination was significantly reduced compared to that in nonrecipients. However, when P14 cells were transferred on day 3 or 5 p.i., no difference in acute or chronic disease was observed compared to that in nonrecipients. Protection in mice receiving P14 splenocytes prior to infection correlated with a robust gp33-specific immune response that was not observed in mice receiving the later transfers. Thus, an early robust CD8+ T-cell response was necessary to reduce virus replication and spread, specifically to the spinal cord, which protected against demyelination in the chronic phase of the disease.

* Corresponding author. Mailing address: Department of Microbiology, University of Pennsylvania, School of Medicine, 36th St. and Hamilton Walk, Philadelphia, PA 19104-6076. Phone: (215) 898-8013. Fax: (215) 573-4858. E-mail: weisssr{at}mail.med.upenn.edu.

Journal of Virology, March 2005, p. 3370-3381, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3370-3381.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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