Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations
Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations
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DOI：
10.1097/00002371-200111000-00007
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发表时间：
2001-11-01
影响因子：
3.9
通讯作者：
Schmidt-Wolf, IGH
中科院分区：
文献类型：
--
作者：
Märten, A;Ziske, C;Schmidt-Wolf, IGH
树突状细胞（Dendritic cells，DC）是主要的抗原提呈细胞，具有捕获和加工肿瘤抗原、表达淋巴细胞共刺激分子、分泌细胞因子等功能，可启动免疫应答。在这里，作者测试了尼古丁诱导的杀伤（CIK）细胞的作用，包括CD 3（+）CD 56（+）细胞（自然杀伤T细胞），关于它们的免疫调节DC的能力。细胞因子诱导的杀伤细胞与自体外周血单个核细胞DC共培养。使用流式细胞术测量两个人群的典型市场的表达，并使用酶联免疫吸附测定法测定白细胞介素（IL）-12的分泌。进行细胞毒性测定以研究IL-12的作用和细胞-细胞相互作用的重要性。考虑到这一点，IL-12和CD 40的受体被阻断，并用细胞培养插入物进行共培养。CIK细胞的共培养导致DC培养物中DC特异性、共刺激和抗原呈递分子的显著增加。此外，共培养导致DC的IL-12分泌显著增加，CIK细胞对癌细胞的细胞毒活性显著增加。阻断IL-12摄取可降低CIK细胞的细胞溶解活性。细胞因子的分泌对CIK细胞的活化是重要的，并且DCs和效应细胞之间的细胞相互作用引起更高的细胞溶解能力。DCs与CIK细胞相互作用引起两个群体表面分子表达的变化，导致IL-12分泌增加，并呈现出改善的细胞毒活性。自然杀伤T细胞亚群似乎是这种效应的原因。因此，DC与CIK细胞的共培养可能对癌症患者的免疫方案产生重大影响。
Dendritic cells (DCs) are major antigen-presenting cells, They are capable of capturing and processing tumor antigens, expressing lymphocyte costimulatory molecules, and secreting cytokines to initiate immune responses. Here, the authors tested the effect of cytokine-induced killer (CIK) cells, a population that includes CD3(+)CD56(+) cells (natural killer T cells), with regard to their capacity to immuno-modulate DCs. Cytokine-induced killer cells were cocultured with autologous DCs Generated from peripheral blood mononuclear cells. Expression of markets typical for both populations was measured using flow cytometry, and secretion of interleukin (IL)-12 was determined using enzyme-linked immunosorbent assays. Cytotoxicity assays were performed to investigate the role of IL-12 and the importance of cell-cell interactions. Considering this, receptors for IL-12 and CD40 were blocked and cocultures were performed with cell culture inserts. Coculture of CIK cells led to a significant increase of DC-specific, costimulatory, and antigen-presenting molecules in DC cultures. In addition, coculture resulted in a dramatically increase of IL-12 secretion by DCs and to a significant increase in cytotoxic activity of CIK cells toward carcinoma cells. Blockage of IL-12 uptake decreased the cytolytic activity of CIK cells. Cytokine secretion was shown to be important for activation of CIK cells, and also cellular interactions between DCs and effector cells caused a higher cytolytic capacity. Interactions between DCs and CIK cells caused changes in the surface molecule expression of both populations, led to an increase of IL-12 secretion, and rendered an improved cytotoxic activity. The natural killer T cell subpopulation seems to be responsible for this effect. Therefore, coculture of DCs with CIK cells may have a major impact on immunotherapeutic protocols for patients with cancer.