Interferon-gamma-mediated site-specific clearance of alphavirus from CNS neurons

Recovery from viral encephalomyelitis requires immune-mediated noncytolytic clearance from neurons by mechanisms assumed to be the same for all neuron s. In alphavirus encephalomyelitis, antibody clears infectious virus from n eurons in all regions of the central nervous system (CNS), but CD8 T cells contribute to elimination of viral RNA. To understand the role of T cells i n clearance, we infected antibody knockout mice with Sindbis virus. Virus w as cleared from spinal cord and brain stem neurons, but not from cortical n eurons, and required both CD4 and CD8 T cells. Infection with cytokine-expr essing recombinant viruses suggested that T cells used interferon-gamma, bu t not tumor necrosis factor alpha, in clearing virus and that populations o f neurons differ in responsiveness to this effector pathway.