Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
Mol Immunol. 2011 Sep;48(15-16):1744-52. doi: 10.1016/j.molimm.2011.04.018. Epub 2011 Jun 1.
To understand the interaction of dendritic cells (DCs) with cancer cells, we investigated molecular changes in DCs following co-culture with cancer cells. DCs co-cultured with Jurkat cancer cells showed remarkable down-regulation of MHC class I molecules, while DCs co-cultured with MCF-7 cancer cells showed minimal changes. Interestingly, down-regulation of MHC class I on DCs was not observed upon treatment with Jurkat cell lysate or culture supernatant, suggesting the importance of direct cell-cell interactions. The expressions of CD40, CD80, CD83, MHC class II, and IL-12p40 on DCs co-cultured with Jurkat cells were only slightly affected. In contrast, DCs co-cultured with MCF-7 cells showed increased expressions of CD80, CD83, CD86, and IL-12p40. Furthermore, DCs co-cultured with Jurkat cells showed a down-regulation of low molecular weight polypeptides (LMP) 7, and of transporter associated with antigen processing (TAP) 1 and 2 at the mRNA expression level. LMP7, TAP2 and β2-microglobulin (β2M) were also down-regulated at the protein level. We further demonstrated how altered expression of MHC class I on DCs caused by co-culture with cancer cells affected autologous CD8(+) T cells, using the model MHC class I-presented HSV antigen. We found that DCs that had been HSV-treated and co-cultured with Jurkat cells showed a reduced potency to activate CD8(+) T cells. In contrast, HSV-treated DCs that had been co-cultured with MCF-7 cells induced activation of CD8(+) T cells, including high expression of CD25, CD69, granzyme B and cytokines, TNF-α and IFN-γ.
为了了解树突状细胞（DC）与癌细胞的相互作用，我们研究了 DC 与癌细胞共培养后分子的变化。与 Jurkat 癌细胞共培养的 DC 显著下调 MHC Ⅰ类分子，而与 MCF-7 癌细胞共培养的 DC 变化最小。有趣的是，Jurkat 细胞裂解物或培养上清液处理后并未观察到 DC 上 MHC Ⅰ类分子的下调，这表明直接的细胞-细胞相互作用很重要。与 Jurkat 细胞共培养的 DC 上 CD40、CD80、CD83、MHC Ⅱ类和 IL-12p40 的表达仅受到轻微影响。相比之下，与 MCF-7 细胞共培养的 DC 上 CD80、CD83、CD86 和 IL-12p40 的表达增加。此外，与 Jurkat 细胞共培养的 DC 表现出低分子量多肽（LMP）7、抗原加工相关转运体（TAP）1 和 2 的 mRNA 表达水平下调。LMP7、TAP2 和β2-微球蛋白（β2M）在蛋白水平也下调。我们进一步通过 MHC Ⅰ类呈递 HSV 抗原的模型，证明了与癌细胞共培养后 DC 上 MHC Ⅰ类分子表达的改变如何影响自体 CD8(+)T 细胞。我们发现，与 Jurkat 细胞共培养的经 HSV 处理的 DC 激活 CD8(+)T 细胞的能力降低。相比之下，与 MCF-7 细胞共培养的经 HSV 处理的 DC 诱导 CD8(+)T 细胞的激活，包括 CD25、CD69、颗粒酶 B 和细胞因子 TNF-α 和 IFN-γ 的高表达。
