T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function.
T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function.
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DOI：
10.4049/jimmunol.163.9.5020
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发表时间：
1999-11
影响因子：
4.4
通讯作者：
Sherven P Sharma;M. Stolina;Ying Q Lin;B. Gardner;Patrice W. Miller;M. Kronenberg;S. Dubinett
中科院分区：
文献类型：
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作者：
Sherven P Sharma;M. Stolina;Ying Q Lin;B. Gardner;Patrice W. Miller;M. Kronenberg;S. Dubinett
我们先前已经发现，人类肺癌在体外可以有效地诱导T淋巴细胞产生IL-10。为了评估增强的T细胞来源的IL-10对体内抗肿瘤免疫的影响，我们使用了在IL-2启动子控制下表达IL-10的转基因小鼠。我们以前已经证明，在IL-10转基因小鼠中，Lewis肺癌细胞(3LL)比对照小鼠具有更具侵袭性的生长潜力。在这项研究中，我们证明了将IL-10转基因小鼠的T细胞转移到对照仔鼠身上，转移了IL-10的免疫抑制效应，并导致了3LL肿瘤的促进生长。除了T细胞介导的免疫功能的改变，来自IL-10转基因小鼠的专业APC被发现显著抑制了诱导MHC同种异体反应、CTL反应和IL-12产生的能力。来自IL-10转基因小鼠的肿瘤抗原冲击的树突状细胞也不能产生抗肿瘤反应。这些结果表明，由于T细胞和APC功能的缺陷，T细胞来源的IL-10水平的增加严重损害了体内的抗肿瘤免疫。
We have found previously that human lung cancers potently induce T lymphocyte IL-10 production in vitro. To assess the impact of enhanced T cell-derived IL-10 on antitumor immunity in vivo, we utilized transgenic mice expressing IL-10 under the control of the IL-2 promoter. We have shown previously that Lewis lung carcinoma cells (3LL) have more aggressive growth potential in IL-10 transgenic mice compared with control littermates. In this study, we show that transfer of T cells from IL-10 transgenic mice to control littermates transferred the IL-10 immunosuppressive effect and led to enhanced 3LL tumor growth. In addition to changes in T cell-mediated immunity, professional APC from IL-10 transgenic mice were found to have significantly suppressed capacity to induce MHC alloreactivity, CTL responses, and IL-12 production. Tumor Ag-pulsed dendritic cells from IL-10 transgenic mice also failed to generate antitumor reactivity. These results suggest that increased levels of T cell-derived IL-10 severely impair antitumor immunity in vivo, due to defects in both T cell and APC function.