📄 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-γ 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. © 2003 Elsevier Science (USA).

keywords 🔗 present study (186) 🔗 nervous system (116) 🔗 white matter (16) 🔗 hepatitis virus (437) 🔗 mouse hepatitis (371) 🔗 significant differences (40) 🔗 central nervous (112) 🔗 adoptive transfer (14)

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