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用维生素C处理小鼠骨髓来源的树突状细胞可增强这些细胞在体内产生CD8(+)记忆性T细胞的能力。

Vitamin C treatment of mouse bone marrow-derived dendritic cells enhanced CD8(+) memory T cell production capacity of these cells in vivo.

作者信息

Jeong Young-Joo, Kim Jin-Hee, Hong Jun-Man, Kang Jae Seung, Kim Hang-Rae, Lee Wang Jae, Hwang Young-il

机构信息

Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.

Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.

出版信息

Immunobiology. 2014 Jul;219(7):554-64. doi: 10.1016/j.imbio.2014.03.006. Epub 2014 Mar 20.

DOI:10.1016/j.imbio.2014.03.006
PMID:24698552
Abstract

Vitamin C has been found to stimulate dendritic cells (DCs) to secrete more IL-12 and thereby drive naïve CD4(+) T cells to differentiate into Th1 cells. In the present study, we evaluated the effect of these vitamin C-treated DCs on CD8(+) T cell differentiation both in vitro and in vivo. Mouse bone marrow-derived DCs were prepared in the presence of GM-CSF and IL-15. With vitamin C treatment, these DCs, when LPS-stimulated, secreted more IL-12p70 and IL-15 than did untreated DCs. And when co-cultured with T cells, they yielded a higher frequency of IFN-γ(+) CD8(+) T cells. Moreover, we found that administering vitamin C-treated and tumor lysate-loaded DCs into mice yielded a higher frequency of CD44(high) CD62L(low) CD8(+) effector and effector memory T cells, which showed an increased ex vivo killing effect of the tumor cells. These DCs also elicited enhanced protective effects against inoculated tumor cells, most probably by way of the increased cytotoxic T cells, as was revealed by the decreased growth of the inoculated tumor cells in these mice. This ex vivo vitamin C treatment effect on DCs can be considered as a strategy for boosting DC vaccination potency against tumors.

摘要

已发现维生素C可刺激树突状细胞(DCs)分泌更多白细胞介素-12(IL-12),从而促使初始CD4(+) T细胞分化为Th1细胞。在本研究中,我们评估了这些经维生素C处理的DCs在体外和体内对CD8(+) T细胞分化的影响。在粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-15(IL-15)存在的情况下制备小鼠骨髓来源的DCs。经维生素C处理后,这些DCs在受到脂多糖(LPS)刺激时,比未处理的DCs分泌更多的IL-12p70和IL-15。当与T细胞共培养时,它们产生的干扰素-γ(IFN-γ)(+) CD8(+) T细胞频率更高。此外,我们发现将经维生素C处理且负载肿瘤裂解物的DCs注射到小鼠体内,可产生更高频率的CD44(高) CD62L(低) CD8(+)效应性和效应记忆性T细胞,这些细胞对肿瘤细胞的体外杀伤作用增强。这些DCs还对接种的肿瘤细胞产生了更强的保护作用,很可能是通过增加细胞毒性T细胞实现的,这从这些小鼠体内接种肿瘤细胞生长减缓可以看出。这种体外维生素C对DCs的处理效果可被视为一种提高DC疫苗对肿瘤免疫效力的策略。

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