Märten A, Ziske C, Schöttker B, Renoth S, Weineck S, Buttgereit P, Schakowski F, von Rücker A, Sauerbruch T, Schmidt-Wolf I G
Medizinische Klinik und Poliklinik I, Allgemeine Innere Medizin, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
J Immunother. 2001 Nov-Dec;24(6):502-10. doi: 10.1097/00002371-200111000-00007.
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 immunomodulate DCs. Cytokine-induced killer cells were cocultured with autologous DCs generated from peripheral blood mononuclear cells. Expression of markers 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.
树突状细胞（DCs）是主要的抗原呈递细胞。它们能够捕获和处理肿瘤抗原，表达淋巴细胞共刺激分子，并分泌细胞因子以启动免疫反应。在此，作者测试了细胞因子诱导的杀伤细胞（CIK），即包括CD3 + CD56 +细胞（自然杀伤T细胞）的群体，对其免疫调节DCs能力的影响。将细胞因子诱导的杀伤细胞与从外周血单核细胞产生的自体DCs共培养。使用流式细胞术测量两个群体典型标志物的表达，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的作用和细胞间相互作用的重要性。考虑到这一点，阻断IL-12和CD40的受体，并使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DCs分泌IL-12显著增加，并导致CIK细胞对癌细胞的细胞毒性活性显著增加。阻断IL-12摄取降低了CIK细胞的溶细胞活性。已表明细胞因子分泌对CIK细胞的激活很重要，并且DCs与效应细胞之间的细胞相互作用也导致更高的溶细胞能力。DCs与CIK细胞之间的相互作用导致两个群体的表面分子表达发生变化，导致IL-12分泌增加，并提高了细胞毒性活性。自然杀伤T细胞亚群似乎负责这种效应。因此，DCs与CIK细胞的共培养可能对癌症患者的免疫治疗方案产生重大影响。
