CD4+ T cells are not required for the induction of dengue virus-specific CD8+ T cell or antibody responses but contribute to protection after vaccination.
CD4+ T cells are not required for the induction of dengue virus-specific CD8+ T cell or antibody responses but contribute to protection after vaccination.
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DOI：
10.4049/jimmunol.1001709
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Shresta S
中科院分区：
文献类型：
--
作者：
Yauch LE;Prestwood TR;May MM;Morar MM;Zellweger RM;Peters B;Sette A;Shresta S
T细胞在宿主对登革病毒(DENV)感染反应中的作用还不是很清楚。此前，我们使用小鼠传代的登革热病毒株和对登革热病毒感染敏感的干扰素-α/βR−/−C57BL/6小鼠，证明了在初次感染登革热病毒期间对CD8+T细胞的保护作用。在这里，我们研究了CD4+T细胞在原发DENV感染中的作用。鉴定了来自3个非结构DENV蛋白的4个I-Ab限制性表位。病毒感染后CD_4~+T细胞扩增和活化，高峰出现在第7天。DEN病毒特异性CD_4~+T细胞表达细胞内干扰素-γ、肿瘤坏死因子、IL-2和CD40L，并在体内杀伤多肽冲击的靶细胞。令人惊讶的是，在DENV感染前清除CD4+T细胞对病毒载量没有影响。与此观察一致的是，CD4+T细胞耗尽并不影响DENV特异性的IgG或IgM抗体效价或其中和活性，也不影响DENV特异性的CD8+T细胞反应。然而，在感染前用CD4+T细胞表位免疫可显著降低病毒载量。因此，我们得出结论，尽管控制原发DENV感染不需要CD4+T细胞，但免疫诱导它们可以有助于病毒清除。这些发现表明，通过接种疫苗诱导抗DENV CD4+T细胞反应可能是有益的。
The contribution of T cells to the host response to dengue virus (DENV) infection is not well understood. We previously demonstrated a protective role for CD8+ T cells during primary DENV infection using a mouse-passaged DENV strain and IFN-α/βR−/− C57BL/6 mice, which are susceptible to DENV infection. Here we examine the role of CD4+ T cells during primary DENV infection. Four I-Ab-restricted epitopes derived from three of the non-structural DENV proteins were identified. CD4+ T cells expanded and were activated after DENV infection, with peak activation occurring on day 7. The DENV-specific CD4+ T cells expressed intracellular IFN-γ, TNF, IL-2, and CD40L, and killed peptide-pulsed target cells in vivo. Surprisingly, depletion of CD4+ T cells before DENV infection had no effect on viral loads. Consistent with this observation, CD4+ T cell depletion did not affect the DENV-specific IgG or IgM Ab titers or their neutralizing activity, or the DENV-specific CD8+ T cell response. However, immunization with the CD4+ T cell epitopes before infection resulted in significantly lower viral loads. Thus, we conclude that whereas CD4+ T cells are not required for controlling primary DENV infection, their induction by immunization can contribute to viral clearance. These findings suggest inducing anti-DENV CD4+ T cell responses by vaccination may be beneficial.
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影响因子：
6.7
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