Interleukin-10 increases Th1 cytokine production and cytotoxic potential in human papillomavirus-specific CD8+ cytotoxic T lymphocytes
Interleukin-10 increases Th1 cytokine production and cytotoxic potential in human papillomavirus-specific CD8+ cytotoxic T lymphocytes
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DOI：
10.1128/jvi.74.10.4729-4737.2000
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发表时间：
2000-05-01
影响因子：
5.4
通讯作者：
Cannon, MJ
中科院分区：
文献类型：
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作者：
Santin, AD;Hermonat, PL;Cannon, MJ
白细胞介素-10（IL-10）由于其抑制巨噬细胞依赖性抗原呈递、T细胞增殖和Th 1细胞因子分泌的能力而被广泛认为是免疫抑制性细胞因子。然而，一些研究已经挑战了IL-10仅作为免疫抑制细胞因子的看法。作为对宫颈癌患者过继输血增强人乳头瘤病毒E7特异性CD 8（+）细胞毒性T淋巴细胞（CTL）细胞毒性活性的研究的一部分，我们发现IL-10与IL-2的组合与其他几种组合不同，包括IL-2与IL-12、γ干扰素（IFN-γ）和IL-10。IFN-γ、肿瘤坏死因子α和转化生长因子β能够持续增加细胞毒性。细胞毒活性的增强与荧光激活细胞分选仪检测到的穿孔素细胞质积累的显著增加相关。暴露于IL-10的CTL增加了CD 8异源二聚体辅助受体和CD 56分子的α和β链的表面表达。更重要的是，发现在抗原刺激后IL-10与IL-2的组合施用一致地增加了Th 1细胞因子的细胞内表达（即，IFN-γ和IL-2）与单独IL-2中培养的对照CD 8（+）T细胞的结果进行比较。在动力学研究中，与对照培养物相比，在刺激后的早期和晚期时间点，在含有IL-10的CTL培养物中增殖、细胞内穿孔素水平、细胞毒性活性和IFN-γ表达一致升高。相反，细胞内IL-2表达仅在自体肿瘤细胞或固相抗CD 3抗体刺激后的早期时间点持续增加。总之，这些数据支持IL-10与IL-2组合用于肿瘤特异性CTL的体外扩增和增强以用于癌症治疗的临床用途。
Interleukin-10 (IL-10) is widely known as an immunosuppressive cytokine by virtue of its ability to inhibit macrophage-dependent antigen presentation, T-cell proliferation, and Th1 cytokine secretion. However, several studies have challenged the perception of IL-10 solely as an immunosuppressive cytokine. As part of an investigation on potentiation of the cytotoxic activity of human papillomavirus E7-specific CD8(+) cytotoxic T lymphocytes (CTL) for adoptive transfusions to cervical cancer patients, we found that IL-10 in combination with IL-2, unlike several other combinations, including IL-2 with IL-12, gamma interferon (IFN-gamma), tumor necrosis factor alpha, and transforming growth factor beta, was able to consistently increase cytotoxicity. This augmentation in cytotoxic activity correlated with a significant increase in the cytoplasmic accumulation of perforin as detected by fluorescence-activated cell sorter. Surface expression of both the alpha and beta chains of the CD8 heterodimeric coreceptor and CD56 molecules was increased by exposure of CTL to IL-10. More importantly, found that administration of IL-10 in combination with IL-2 after antigen stimulation consistently increased the intracellular expression of Th1 cytokines (i.e., IFN-gamma and IL-2) compared to results for control CD8(+) T cells cultured in IL-2 alone. In kinetic studies, proliferation, intracellular perforin levels, cytotoxic activity, and IFN-gamma expression were consistently elevated in CTL cultures containing IL-10 compared to control cultures, both at early and late time points following stimulation. In contrast, intracellular IL-2 expression was consistently increased only at early time points following stimulation with autologous tumor cells or solid-phase anti-CD3 antibody. Taken together, these data support the use of IL-10 in combination with IL-2 for the in vitro expansion and potentiation of tumor-specific CTL for clinical use in the therapy of cancer.