期刊
JOURNAL OF VIROLOGY
卷 81, 期 18, 页码 9801-9811出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00941-07
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资金
- NIAID NIH HHS [U54 AI057160, AI 061373, U54 AI 057160, U54 AI 057160-05, U01 AI061373] Funding Source: Medline
- NINDS NIH HHS [K02 NS045607, NS 045607, R01 NS052632, NS 052632] Funding Source: Medline
Recent studies have established a protective role for T cells during primary West Nile virus (WNV) infection. Binding of CD40 by CD40 ligand (CD40L) on activated CD4(+) T cells provides an important costimulatory signal for immunoglobulin class switching, antibody affinity maturation, and priming of CD8(+) T-cell responses. We examined here the function of CD40-dependent interactions in limiting primary WNV infection. Compared to congenic wild-type mice, CD40(-)/(-) mice uniformly succumbed to WNV infection. Although CD40(-)/(-) mice produced low levels of WNV-specific immunoglobulin M (IgM) and IgG, viral clearance from the spleen and serum was not altered, and CD8(+) T-cell priming in peripheral lymphoid tissues was normal. Unexpectedly, CD8(+) T-cell trafficking to the central nervous system (CNS) was markedly impaired in CD40(-)/(-) mice, and this correlated with elevated WNV titers in the CNS and death. In the brains of CD40(-)/(-) mice, T cells were retained in the perivascular space and did not migrate into the parenchyma, the predominant site of WNV infection. In contrast, in wild-type mice, T cells trafficked to the site of infection in neurons. Beside its role in maturation of antibody responses, our experiments suggest a novel function of CD40-CD40L interactions: to facilitate T-cell migration across the blood-brain barrier to control WNV infection.
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