Functional analysis of the CC chemokine receptor 5 (CCR5) on virus-specific CD8+ T cells following coronavirus infection of the central nervous system.
Intracranial infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a demyelinating disease similar in pathology to the human disease multiple sclerosis (MS). T cells participate in both defense and disease progression following MHV infection. Expression of chemokine receptors on activated T cells is important in allowing these cells to traffic into and accumulate within the central nervous system (CNS) of MHV-infected mice. The present study evaluated the contributions of CCR5 to the activation and trafficking of virus-specific CD8(+) T cells into the MHV-infected CNS mice. Comparable numbers of virus-specific CD8(+) T cells derived from immunized CCR5(+/+) or CCR5(-/-) mice were present within the CNS of MHV-infected RAG1(-/-) mice following adoptive transfer, indicating that CCR5 is not required for trafficking of these cells into the CNS. RAG1(-/-) recipients of CCR5(-/-)-derived CD8(+) T cells exhibited a modest, yet significant (P </= 0.05), reduction in viral burden within the brain which correlated with increased CTL activity and IFN-gamma expression. Histological analysis of RAG1(-/-) recipients of either CCR5(+/+)or CCR5(-/-)-derived CD8(+) T cells revealed only focal areas of demyelination with no significant differences in white matter destruction. These data indicate that CCR5 signaling on CD8(+) T cells modulates antiviral activities but is not essential for entry into the CNS.
Glass
William G
WG
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
Lane
Thomas E
TE
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D006517:Murine hepatitis virus / Q000276:immunology*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*
D019713:Receptors, CCR5; D007371:Interferon-gamma