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J. Virol. doi:10.1128/JVI.01762-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

CD4 T cells contribute to virus control and pathology following CNS infection by neurotropic mouse hepatitis virus

Departments of Neurology, Pathology and Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033

^* To whom correspondence should be addressed. Email: stohlms2{at}ccf.org.

	Abstract

Replication of the neurotropic mouse hepatitis virus strain JHM is primarily controlled by CD8⁺ T cell effectors utilizing IFN- and perforin mediated cytotoxicity. CD4⁺ T cells provide auxiliary function(s) for CD8⁺ T cell survival; however, their direct contribution to control of virus replication and pathology is unclear. To examine a direct role of CD4⁺ T cells in viral clearance and pathology, pathogenesis was compared in mice deficient in both perforin and IFN- selectively reconstituted for these functions via transfer of virus specific memory CD4⁺ T cells. CD4⁺ T cells from immunized wild type, perforin deficient, and IFN- deficient donors all initially reduced virus replication. However, prolonged viral control by IFN- competent donors suggest that IFN- is important for sustained virus control. Local release of IFN- was evident by up-regulation of class II molecules on microglia in recipients of IFN- producing CD4⁺ T cells. CD4⁺ T cell mediated antiviral activity correlated with diminished clinical symptoms, pathology and demyelination. Both wild type donor CD90.1 and recipient CD90.2 CD4⁺ T cells trafficked into the CNS parenchyma and localized to infected white matter, correlating with decreased numbers of virus infected oligodendrocytes in the CNS. These data support a direct, if limited, anti-viral role for CD4⁺ T cells early during acute JHMV encephalomyelitis. Although the antiviral effector mechanism is initially independent of IFN- secretion, sustained control of CNS virus replication by CD4⁺ T cells requires IFN-.