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Journal of Virology, December 2008, p. 12432-12440, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01267-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Memory CD4⁺ T-Cell-Mediated Protection from Lethal Coronavirus Encephalomyelitis

Carine Savarin,¹ Cornelia C. Bergmann,¹ David R. Hinton,² Richard M. Ransohoff,¹ and Stephen A. Stohlman^1*

Department of Neurosciences, NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195,¹ Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033²

Received 18 June 2008/ Accepted 1 October 2008

The antiviral role of CD4⁺ T cells in virus-induced pathologies of the central nervous system (CNS) has not been explored extensively. Control of neurotropic mouse hepatitis virus (JHMV) requires the collaboration of CD4⁺ and CD8⁺ T cells, with CD8⁺ T cells providing direct perforin and gamma interferon (IFN-)-mediated antiviral activity. To distinguish bystander from direct antiviral contributions of CD4⁺ T cells in virus clearance and pathology, memory CD4⁺ T cells purified from wild type (wt), perforin-deficient (PKO), and IFN--deficient (GKO) immune donors were transferred to immunodeficient SCID mice prior to CNS challenge. All three donor CD4⁺ T-cell populations controlled CNS virus replication at 8 days postinfection, indicating IFN-- and perforin-independent antiviral function. Recipients of GKO CD4⁺ T cells succumbed more rapidly to fatal disease than untreated control infected mice. In contrast, wt and PKO donor CD4⁺ T cells cleared infectious virus to undetectable levels and protected from fatal disease. Recipients of all CD4⁺ T-cell populations exhibited demyelination. However, it was more severe in wt CD4⁺ T-cell recipients. These data support a role of CD4⁺ T cells in virus clearance and demyelination. Despite substantial IFN--independent antiviral activity, IFN- was crucial in providing protection from death. IFN- reduced neutrophil accumulation and directed macrophages to white matter but did not ameliorate myelin loss.

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* Corresponding author. Mailing address: Department of Neurosciences, NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195. Phone: (216) 444-9796. Fax: (216) 444-7927. E-mail: stohlms2{at}ccf.org

Published ahead of print on 8 October 2008.

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Journal of Virology, December 2008, p. 12432-12440, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01267-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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