Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
Cell Immunol. 2010;262(1):35-43. doi: 10.1016/j.cellimm.2009.12.005. Epub 2009 Dec 16.
We previously reported that the baculovirus induced a strong host immune response against infections and malignancies. Among the immune cells, the dendritic cells were most strongly infected and activated by the baculovirus, although the exact mechanism remained unclear. Here, we evaluated the non-specific immune responses of bone marrow-derived dendritic cells (BMDCs) after infection by a wild-type baculovirus. MHC class I and II molecules and co-stimulation molecules (CD40, CD80, and CD86) on BMDCs were up-regulated by baculovirus infection. At the same time, the BMDCs produced pre-inflammatory cytokines (IL-6, IL12p70, and TNF-alpha) and IFN-alpha. NK cells showed IFN-gamma production, CD69 up-regulation, and enhanced cytotoxicity when they were co-cultured with baculovirus-infected BMDCs. T cells showed IFN-gamma production, CD69 up-regulation, and cell proliferation. Ex vivo analysis performed in vitro produced similar results. These findings suggested that baculovirus-infected dendritic cells induce non-specific immune responses and can be used as an immunotherapeutic agent against viral infections and malignancies, together with present therapeutic drug regimens.
我们之前曾报道过杆状病毒会引发强烈的宿主免疫反应,以对抗感染和恶性肿瘤。在免疫细胞中,树突状细胞受杆状病毒感染和激活的程度最强,尽管确切的机制仍不清楚。在这里,我们评估了野生型杆状病毒感染后骨髓来源的树突状细胞(BMDCs)的非特异性免疫反应。杆状病毒感染上调了 BMDCs 上的 MHC Ⅰ类和Ⅱ类分子以及共刺激分子(CD40、CD80 和 CD86)。同时,BMDCs 产生了前炎性细胞因子(IL-6、IL12p70 和 TNF-α)和 IFN-α。当与杆状病毒感染的 BMDCs 共培养时,NK 细胞表现出 IFN-γ产生、CD69 上调和增强的细胞毒性。T 细胞表现出 IFN-γ产生、CD69 上调和细胞增殖。体外进行的离体分析产生了类似的结果。这些发现表明,杆状病毒感染的树突状细胞可诱导非特异性免疫反应,并可与现有治疗药物联合用于对抗病毒感染和恶性肿瘤的免疫治疗。