Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China.
Hum Vaccin Immunother. 2012 Sep;8(9):1236-42. doi: 10.4161/hv.21128. Epub 2012 Aug 21.
The aim of this investigation is to look at whether MENK could improve antitumor effect of CD8+T cell elicited by BMDCs. We investigated the effects of MENK on the differentiation, maturation, and functions of murine BMDC loaded with Rac-1 antigens (RG) and CTL of tumor specific immune response elicited by the BMDC in vitro and in vivo. The production of cytokine IL-12 and TNF-α secreted by BMDCs in the presence of MENK was assayed with ELISA and key surface markers of CD40, CD86, CD83 and MHC-II on the BMDCs were analyzed with use of flow cytometry (FCM). In addition, the activities to induce CD8+ T cell proliferation, along with displayed cytotoxicity of the CD8+T cells(CTL) by the BMDCs after treatment with MENK were determined with use of FCM as well as MTS. Our results indicated that MENK induced phenotypic and functional maturation of BMDC loaded with RG antigen, as evidenced by higher level of expression of key surface markers and more production of cytokines. Subsequently, the BMDC activated by MENK intensified immune responses mounted by CTL, resulting in stronger antitumor activity. Our results suggest that MENK could be working as an effective immune adjuvant in vaccine preparation for cancer fight and other immune related diseases. We concluded that MENK could be a positive immune modulator in the improved functions of BMDCs loaded with antigen as well as in CD8+T cell mediated anti-tumor responses.
这项研究的目的是观察 MENK 是否可以提高 BMDC 引发的 CD8+T 细胞的抗肿瘤作用。我们研究了 MENK 对负载 Rac-1 抗原（RG）的 BMDC 分化、成熟和功能的影响，以及体外和体内由 BMDC 引发的肿瘤特异性免疫反应的 CTL。通过 ELISA 检测 BMDC 分泌的细胞因子 IL-12 和 TNF-α的产生，并用流式细胞术（FCM）分析 BMDC 上的关键表面标记物 CD40、CD86、CD83 和 MHC-II。此外，还通过 FCM 和 MTS 测定了经 MENK 处理后 BMDC 诱导 CD8+T 细胞增殖的活性以及 CD8+T 细胞（CTL）的细胞毒性。我们的结果表明，MENK 诱导了负载 RG 抗原的 BMDC 的表型和功能成熟，这表现为关键表面标记物的表达水平更高，细胞因子的产生更多。随后，经 MENK 激活的 BMDC 增强了 CTL 引发的免疫反应，从而增强了抗肿瘤活性。我们的结果表明，MENK 可作为癌症防治和其他免疫相关疾病疫苗制备中的有效免疫佐剂。我们得出结论，MENK 可以作为一种有效的免疫调节剂，改善负载抗原的 BMDC 的功能以及 CD8+T 细胞介导的抗肿瘤反应。
