West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection.
West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection.
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DOI：
10.4049/jimmunol.181.12.8568
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Nikolich-Zugich J
中科院分区：
文献类型：
--
作者：
Brien JD;Uhrlaub JL;Nikolich-Zugich J
CD 4 T细胞已被证明是必要的预防脑炎在西尼罗河病毒感染。然而，抗原特异性CD 4 T细胞保护小鼠免受西尼罗河病毒脑炎的机制仍不完全清楚。与CD 4 T细胞是保护性的，因为它们仅仅维持CD 8 T细胞应答并提高抗体产生的信念相反，我们在这里提供了CD 4 T细胞的直接抗病毒活性的证据，其功能是保护宿主免受西尼罗河病毒脑炎。在过继转移中，初始CD 4 T细胞保护了大量致死性感染的RAG−/−小鼠，证明了CD 4 T细胞的保护作用独立于B细胞和CD 8 T细胞。为了阐明这种保护的机制，我们定义了C57 BL/6（H-2b）小鼠中响应西尼罗病毒感染的CD 4 T细胞的肽特异性，并使用这些肽来表征抗病毒CD 4 T细胞的体内功能。WNV特异性CD 4 T细胞产生IFN-γ和IL-2，但也显示出体内和离体细胞毒性的潜力。此外，使用CD 4表位的肽疫苗接种在免疫活性小鼠中赋予针对致死性西尼罗病毒感染的保护。这些结果证明了抗原特异性CD 4 T细胞的直接效应功能在预防严重西尼罗病毒病中的作用。
CD4 T cells have been shown to be necessary for the prevention of encephalitis during West Nile virus infection. However, the mechanisms used by antigen-specific CD4 T cells to protect mice from West Nile virus encephalitis remain incompletely understood. Contrary to the belief that CD4 T cells are protective because they merely maintain the CD8 T cell response and improve antibody production, we here provide evidence for the direct anti-viral activity of CD4 T cells which functions to protect the host from WNV encephalitis. In adoptive transfers, naïve CD4 T cells protected a significant number of lethally infected RAG−/− mice, demonstrating the protective effect of CD4 T cells independent of B cells and CD8 T cells. To shed light on the mechanism of this protection, we defined the peptide specificities of the CD4 T cells responding to West Nile virus infection in C57BL/6 (H-2b) mice, and used these peptides to characterize the in vivo function of antiviral CD4 T cells. WNV-specific CD4 T cells produced IFN-γ and IL-2, but also showed potential for in vivo and ex vivo cytotoxicity. Furthermore, peptide vaccination using CD4 epitopes conferred protection against lethal West Nile virus infection in immunocompetent mice. These results demonstrate the role of direct effector function of antigen-specific CD4 T cell in preventing severe West Nile virus disease.
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