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Journal of Virology, March 2002, p. 2217-2224, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2217-2224.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Chemokine Expression in the Central Nervous System of Mice with a Viral Disease Resembling Multiple Sclerosis: Roles of CD4+ and CD8+ T Cells and Viral Persistence

*** R. M. Ransohoff,1* T. Wei,1 K. D. Pavelko,2,3 J.-C. Lee,4 P. D. Murray,2,3 and M. Rodriguez2,3

Department of Neurosciences,1 Department of Biostatistics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio,4 Departments of Immunology,2 Neurology, Mayo Clinic and Foundation, Rochester, Minnesota3

Received 17 September 2001/ Accepted 15 November 2001

During the first 45 days after intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV), the levels of mRNAs encoding chemokines MCP-1/CCL2, RANTES/CCL5, and IP-10/CXCL10 in the central nervous system (CNS) are closely related to the sites of virus gene expression and tissue inflammation. In the present study, these chemokines were monitored during the latter 135 days of a 6-month course of TMEV-induced disease in susceptible (PLJ) or resistant (C57BL/6) mice that possessed or lacked either CD4+ or CD8+ T cells. These data were additionally correlated to mouse genotype, virus persistence in the CNS, antiviral antibody titers, mortality, and the severity of neurological disease. Surprisingly, the major determinant of chemokine expression was virus persistence: the factors of susceptible or resistant genotype, severity of neuropathology, and presence or absence of regulatory T cells exerted minimal effects. Our observations indicated that chemokine expression in the CNS in this chronic viral disorder was intrinsic to the CNS innate immune response to infection and was not governed by elements of the adaptive immune system.

* Corresponding author. Mailing address: Department of Neurosciences, The Lerner Research Institute, The Cleveland Clinic Foundation, NC30, 9500 Euclid Ave., Cleveland, OH 44195. Phone: (216) 444-0627. Fax: (216) 444-7927. E-mail: ransohr{at}ccf.org.

Journal of Virology, March 2002, p. 2217-2224, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2217-2224.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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