Functional analysis of the CC chemokine receptor 5 (CCR5) on virus-specific CD8 super(+) 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 super(+) T cells into the MHV-infected CNS mice. Comparable numbers of virus-specific CD8 super(+) T cells derived from immunized CCR5 super(+/+) or CCR5 super(-/-) mice were present within the CNS of MHV-infected RAG1 super(-/-) mice following adoptive transfer, indicating that CCR5 is not required for trafficking of these cells into the CNS. RAG1 super(-/-) recipients of CCR5 super(-/-)-derived CD8 super(+) T cells exhibited a modest, yet significant (P less than or equal to 0.05), reduction in viral burden within the brain which correlated with increased CTL activity and IFN- gamma expression. Histological analysis of RAG1 super(-/-) recipients of either CCR5 super(+/+)or CCR5 super(-/-)-derived CD8 super(+) T cells revealed only focal areas of demyelination with no significant differences in white matter destruction. These data indicate that CCR5 signaling on CD8 super(+) T cells modulates antiviral activities but is not essential for entry into the CNS.