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Journal of Virology, September 2000, p. 7903-7910, Vol. 74, No. 17
Departments of
Neurology1 and Molecular Microbiology
and Immunology,2 Keck School of Medicine,
University of Southern California, Los Angeles, California 90033
Received 6 April 2000/Accepted 8 June 2000
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 locally maintaining T cells was investigated by
infecting mice with either a demyelinating, paralytic (V-1) or
nonpathogenic (V-2) variant of a neurotropic mouse hepatitis virus,
which differ in the ability to persist within the CNS. Class I tetramer
technology revealed more infiltrating virus-specific CD8+ T
cells during acute V-1 compared to V-2 infection. However, both total
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 with an overall progressive loss of both total and
virus-specific CD8+ T cells. 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 completely disappeared from
V-2-infected spinal cords coincident with the absence 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-infected mice. The data indicate that residual virus from a primary
CNS infection is a vital component in mediating local retention of both
CD8+ and CD4+ T cells and that once minimal
thresholds of stimuli are lost, T cells within the CNS cannot survive
in an autonomous fashion.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Role of Viral Persistence in Retaining
CD8+ T Cells within the Central Nervous
System
*
Corresponding author. Mailing address: 1333 San Pablo
St., MCH 142, Los Angeles, CA 90033. Phone: (323) 442-1062. Fax: (323) 225-2369. E-mail: cbergman{at}hsc.usc.edu.
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