Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands.
Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands.
复制标题
巨细胞病毒利用了唾液腺中IL-10介导的免疫调节。
DOI：
10.1084/jem.20062424
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发表时间：
2007-05-14
影响因子：
15.3
通讯作者：
Ware, Carl F
中科院分区：
文献类型：
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作者：
Humphreys, Ian R;de Trez, Carl;Kinkade, April;Benedict, Chris A;Croft, Michael;Ware, Carl F
唾液腺是巨细胞病毒复制和传播到其他宿主的主要场所。尽管通过内脏器官中的强T细胞反应控制病毒感染，但巨细胞病毒复制在小鼠唾液腺中继续，表明病毒利用粘膜微环境。在这里，我们表明，T细胞免疫在唾液腺是有限的诱导表达调节细胞因子白细胞介素（IL）-10的CD 4 T细胞。用拮抗剂抗体阻断IL-10受体（IL-10 R）可显著降低唾液腺中的病毒载量，但在脾脏中则不然。IL-10 R阻断提供的粘膜特异性保护与表达干扰素γ的CD 4 T细胞的积累增加相关，表明IL-10 R信号传导限制效应T细胞分化。与此一致，靶向肿瘤坏死因子受体超家族成员0X 40（TNFRSF 4）的激动剂抗体增强效应T细胞分化并增加产生干扰素γ的T细胞的数量，从而限制唾液腺中的病毒复制。总的来说，这些结果表明，调节效应T细胞分化可以抵消病原体对粘膜的利用，从而限制持续的病毒复制和传播。
The salivary glands represent a major site of cytomegalovirus replication and transmission to other hosts. Despite control of viral infection by strong T cell responses in visceral organs cytomegalovirus replication continues in the salivary glands of mice, suggesting that the virus exploits the mucosal microenvironment. Here, we show that T cell immunity in the salivary glands is limited by the induction of CD4 T cells expressing the regulatory cytokine interleukin (IL)-10. Blockade of IL-10 receptor (IL-10R) with an antagonist antibody dramatically reduced viral load in the salivary glands, but not in the spleen. The mucosa-specific protection afforded by IL-10R blockade was associated with an increased accumulation of CD4 T cells expressing interferon γ, suggesting that IL-10R signaling limits effector T cell differentiation. Consistent with this, an agonist antibody targeting the tumor necrosis factor receptor superfamily member OX40 (TNFRSF4) enhanced effector T cell differentiation and increased the number of interferon γ–producing T cells, thus limiting virus replication in the salivary glands. Collectively, the results indicate that modulating effector T cell differentiation can counteract pathogen exploitation of the mucosa, thus limiting persistent virus replication and transmission.