Type 1 and type 2 CD8+ effector T cell subpopulations promote long-term tumor immunity and protection to progressively growing tumor
Type 1 and type 2 CD8+ effector T cell subpopulations promote long-term tumor immunity and protection to progressively growing tumor
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DOI：
10.4049/jimmunol.164.2.916
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发表时间：
2000-01-15
影响因子：
4.4
通讯作者：
Dutton, RW
中科院分区：
文献类型：
--
作者：
Dobrzanski, MJ;Reome, JB;Dutton, RW
根据细胞因子的分泌，杀伤CD8(+)效应细胞可分为两个亚群。1型CD8(+)T细胞(Tc1)分泌干扰素-γ，而2型CD8(+)T细胞(Tc2)分泌IL-4、IL-5和IL-10。利用OVA转基因的B16肺转移模型，我们评估了过继转移OVA特异性Tc1和Tc2亚群对已建立的肺部恶性肿瘤小鼠的治疗效果。与未治疗的对照组小鼠相比，肿瘤负荷高(5x10(5))的效应细胞治疗小鼠的死亡率显著延迟(p<；0.05)，而接受低(1x10(5))肿瘤负荷治疗的小鼠无限期存活的比例高(70%-90%)。Tc2和Tc1效应细胞的长期保护作用部分依赖于肿瘤负荷水平和效应细胞衍生的IL-4、IL-5和干扰素-γ水平。我们得出结论，Tc1和Tc2效应细胞通过不同的机制提供免疫，从而增强宿主来源的抗肿瘤反应。
Cytolytic CD8(+) effector cells fall into two subpopulations based on cytokine secretion. Type 1 CD8(+) T cells (Tc1) secrete IFN-gamma, whereas type 2 CD8(+) T cells (Tc2) secrete IL-4, IL-5, and IL-10. Using an OVA-transfected B16 lung metastases model, we assessed the therapeutic effects of adoptively transferred OVA-specific Tc1 and Tc2 subpopulations in mice bearing established pulmonary malignancy. Effector cell-treated mice exhibiting high (5 x 10(5)) tumor burdens experienced significant (p < 0.05) delays in mortality compared with those of untreated control mice, whereas high proportions (70-90%) of mice receiving therapy with low (1 x 10(5)) tumor burdens survived indefinitely. Long-term tumor immunity was evident by resistance to lethal tumor rechallenge, heightened levels of systemic OVA Ag-specific CTL responses ex vivo, and detection of long-lived TCR transgene-positive donor cells accompanied by an elevation in the total numbers of CD8(+) CD44(high) activated and/or memory T cells at sites of tumor growth, Long-lasting protection by Tc2 and Tc1 effector cells were dependent, in part, on both the level of tumor burden and effector cell-derived IL-4, IL-5, and IFN-gamma respectively. We conclude that Tc1 and Tc2 effector cells provide immunity by different mechanisms that subsequently potentiate host-derived antitumor responses.