J Virol 2002 Mar;76(5):2217-24
Ransohoff RM, Wei T, Pavelko KD, Lee JC, Murray PD, Rodriguez M.
Department of Neurosciences. Department of Biostatistics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio. Departments of Immunology. Neurology, Mayo Clinic and Foundation, Rochester, Minnesota.
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.