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Journal of Virology, December 2003, p. 13323-13334, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13323-13334.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

CD8+ T Cells Mediate Recovery and Immunopathology in West Nile Virus Encephalitis

Yang Wang, Mario Lobigs, Eva Lee, and Arno Müllbacher*

Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia

Received 27 May 2003/ Accepted 10 September 2003

C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (108 PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (103 PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8+, but not CD4+, T cells. CD8+ T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8+ T-cell-deficient mice infected with 103 PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8+ T cells are involved in both recovery and immunopathology in WNV infection.

* Corresponding author. Mailing address: Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University, P.O. Box 334, Canberra ACT 2601, Australia. Phone: 61-2-6125-4392. Fax: 61-2-6248-6271. E-mail: arno.mullbacher{at}anu.edu.au.

Journal of Virology, December 2003, p. 13323-13334, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13323-13334.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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