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) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System1
*
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697; and
Department of Immunology, The Lerner Research Institute, Cleveland, OH 44195
Induction of a Th1 immune response against viral infection of the
CNS is important in contributing to viral clearance. The present
studies demonstrate a role for the T cell chemoattractant chemokine Mig
(monokine induced by IFN-
) in contributing to a Th1 response against
mouse hepatitis virus infection of the CNS. Analysis of the kinetics of
Mig expression revealed mRNA transcripts present at days 7 and 12
postinfection (p.i.) but not early (day 2) or late (day 35) in the
infection. To determine functional significance, mouse hepatitis
virus-infected mice were treated with anti-Mig antisera, and the
severity of disease was evaluated. Such treatment resulted in a marked
increase in mortality that correlated with a >3 log increase in viral
burden within the brains as compared with control mice treated with
normal rabbit serum. Anti-Mig-treated mice displayed a significant
decrease (p < 0.005) in CD4+ and
CD8+ T cell recruitment into the CNS as compared with
normal rabbit serum-treated mice. In addition, anti-Mig treatment
resulted in a significant decrease (p < 0.05) in
levels of IFN- and IFN-
that coincided with increased
(p < 0.02) expression of the anti-inflammatory
Th2 cytokine IL-10 within the CNS. Collectively, these data indicate
that Mig is important in contributing to host defense by promoting a
protective Th1 response against viral infection of the
CNS.
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