CD4+ T-cell responses are required for clearance of West Nile virus from the central nervous system

Elizabeth M. Sitati, Michael S. Diamond

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168 Scopus citations


Although studies have established that innate and adaptive immune responses are important in controlling West Nile virus (WNV) infection, the function of CD4+ T lymphocytes in modulating viral pathogenesis is less well characterized. Using a mouse model, we examined the role of CD4+ T cells in coordinating protection against WNV infection. A genetic or acquired deficiency of CD4+ T cells resulted in a protracted WNV infection in the central nervous system (CNS) that culminated in uniform lethality by 50 days after infection. Mice surviving past day 10 had high-level persistent WNV infection in the CNS compared to wild-type mice, even 45 days following infection. The absence of CD4+ T-cell help did not affect the kinetics of WNV infection in the spleen and serum, suggesting a role for CD4-independent clearance mechanisms in peripheral tissues. WNV-specific immunoglobulin M (IgM) levels were similar to those of wild-type mice in CD4-deficient mice early during infection but dropped ∼20-fold at day 15 postinfection, whereas IgG levels in CD4-deficient mice were -100- to 1,000-fold lower than in wild-type mice throughout the course of infection. WNV-specific CD8+ T-cell activation and trafficking to the CNS were unaffected by the absence of CD4+ T cells at day 9 postinfection but were markedly compromised at day 15. Our experiments suggest that the dominant protective role of CD4+ T cells during primary WNV infection is to provide help for antibody responses and sustain WNV-specific CD8+ T-cell responses in the CNS that enable viral clearance.

Original languageEnglish
Pages (from-to)12060-12069
Number of pages10
JournalJournal of virology
Issue number24
StatePublished - Dec 2006

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