Role of viral persistence in retaining CD8(+) T cells within the central nervous system

The continued presence of virus-specific CD8(+) T cells within the central nervous system (CNS) following resolution of acute viral encephalomyelitis implicates organ-specific retention. The role of viral persistence in local ly maintaining T cells was investigated by infecting mice with either a dem yelinating, paralytic (V-1) or nonpathogenic (V-2) variant of a neurotropic mouse hepatitis virus, which differ in the ability to persist within the C NS. Class I tetramer technology revealed more infiltrating virus-specific C D8(+) T cells during acute V-1 compared to V-2 infection. However, both tot al and virus-specific CD8(+) T cells accumulated at similar peak levels in spinal cords by day 10 postinfection (p.i.). Decreasing viral RNA levels in both brains and spinal cords following initial virus clearance coincided w ith an overall progressive loss of both total and virus-specific CD8(+) T c ells. By 9 weeks p.i., T cells had largely disappeared from brains of both infected groups, consistent with the decline of viral RNA. T cells also com pletely disappeared from V-2-infected spinal cords coincident with the abse nce of viral RNA. By contrast, a significant number of CD8(+) T cells which contained detectable viral RNA were recovered from spinal cords of V-1-inf ected mice. The data indicate that residual virus from a primary CNS infect ion is a vital component in mediating local retention of both CD8(+) and CD 4(+) T cells and that once minimal thresholds of stimuli are lost, T cells within the CNS cannot survive in an autonomous fashion.