Department of Haematology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Immunology. 2010 May;130(1):137-49. doi: 10.1111/j.1365-2567.2010.03220.x. Epub 2010 Feb 26.
Studies in mice have shown that CD70 on dendritic cells (DCs) is sufficient to convert T-cell tolerance into immunity and hence induce anti-tumour immune responses. Therefore, it is important to investigate (i) optimal stimuli to induce CD70 on human monocyte-derived DCs (MoDCs), which are widely used for tumour immunotherapy, and (ii) the role of CD70 in functional differentiation of naive CD4(+) and CD8(+) T cells stimulated with MoDCs. We show that interferon-alpha (IFN-alpha) is a key cytokine to differentiate monocytes into DCs with the capacity to express CD70 upon maturation. CD70 expression on IFN-alpha-induced MoDCs was elicited by different categories of maturation-inducing factors (Toll-like receptor ligands, CD40 ligand and pro-inflammatory mediators), among which prostaglandin E(2) was most effective. Naive T cells stimulated with MoDCs also expressed CD70. Stimulation with MoDCs promoted naive CD4(+) T cells to acquire the ability to produce T helper type 1 and 2 cytokines in a CD70-dependent manner. In contrast, the CD70-CD27 interaction diminished the production of an immunoregulatory cytokine IL-10. The CD27 signal did not play a dominant role in the induction of effector molecules in naive CD8(+) T cells during the stimulation with MoDCs. This study adds a novel function to the versatile cytokines, type I IFNs, that is, the induction of CD70 on MoDCs. CD70 promotes naive CD4(+) T cells to acquire immunostimulatory activity through the DC-T-cell and T-cell-T-cell interactions during the stimulation with MoDCs. Hence, the CD70-CD27 interaction may play an important role in inducing effective immune responses in DC-based immunotherapy.
在小鼠中的研究表明，树突状细胞（DC）上的 CD70 足以将 T 细胞耐受转化为免疫，从而诱导抗肿瘤免疫反应。因此，重要的是要研究（i）最佳刺激物以诱导广泛用于肿瘤免疫治疗的人单核细胞衍生的 DC（MoDC）上的 CD70，以及（ii）CD70 在 MoDC 刺激的幼稚 CD4（+）和 CD8（+）T 细胞的功能分化中的作用。我们表明，干扰素-α（IFN-α）是一种关键细胞因子，可将单核细胞分化为具有成熟时表达 CD70 能力的 DC。IFN-α 诱导的 MoDC 上的 CD70 表达是由不同类别的成熟诱导因子（Toll 样受体配体、CD40 配体和促炎介质）引起的，其中前列腺素 E（2）最有效。用 MoDC 刺激的幼稚 T 细胞也表达 CD70。MoDC 的刺激以 CD70 依赖性方式促进幼稚 CD4（+）T 细胞获得产生辅助性 T 细胞 1 和 2 细胞因子的能力。相比之下，CD70-CD27 相互作用减少了免疫调节细胞因子 IL-10 的产生。在 MoDC 刺激期间，CD27 信号在诱导幼稚 CD8（+）T 细胞中的效应分子中不起主导作用。这项研究为多功能细胞因子 I 型 IFNs 添加了一个新的功能，即 MoDC 上的 CD70 诱导。CD70 通过 MoDC 刺激期间的 DC-T 细胞和 T 细胞-T 细胞相互作用，促进幼稚 CD4（+）T 细胞获得免疫刺激活性。因此，CD70-CD27 相互作用可能在基于 DC 的免疫治疗中诱导有效免疫反应中发挥重要作用。
