Tomiyama Mai, Takahara Masashi, Egawa Kohji, Nieda Mie
Yokohama City University, School of medicine, 3-9 Fukura, Kanazawa-ku, Yokohama, Japan.
Anticancer Res. 2004 Sep-Oct;24(5C):3327-33.
For successful dendritic cell (DC)-based immunotherapy, it is critical to identify the most potent stage of human DCs, including immature DCs (imDCs) and mature DCs (mDCs).
imDCs were obtained by culturing monocytes in the presence of GM-CSF and IL-4 for 5- 7 days and imDCs were further cultured for 24-48 h in the presence of TNFalpha, IL-6, IL-1beta and PGE2 to obtain mDCs. Melan-A- and EBV (BRF1) peptides were used and the frequency of antigen-specific CD8+ T cells was assessed using appropriate tetramers.
mDCs were potent antigen-presenting cells for the induction and proliferation of antigen-specific naive and memory CD8+ T cells and may overcome regulatory functions that suppress antigen-specific CD8+ T cells.
Our findings that mDCs can efficiently expand antigen-specific naive and memory CD8 + T cells have important implications in the development of vaccination strategies and support the use of antigen-loaded mature DCs in human clinical trials
对于基于树突状细胞(DC)的成功免疫治疗而言,识别人类DC最有效的阶段至关重要,包括未成熟DC(imDC)和成熟DC(mDC)。
通过在GM-CSF和IL-4存在的情况下培养单核细胞5至7天获得imDC,然后在TNFα、IL-6、IL-1β和PGE2存在的情况下将imDC进一步培养24至48小时以获得mDC。使用Melan-A和EBV(BRF1)肽,并使用适当的四聚体评估抗原特异性CD8 + T细胞的频率。
mDC是诱导和增殖抗原特异性初始和记忆CD8 + T细胞的有效抗原呈递细胞,并且可能克服抑制抗原特异性CD8 + T细胞的调节功能。
我们的研究结果表明,mDC可以有效地扩增抗原特异性初始和记忆CD8 + T细胞,这对疫苗接种策略的发展具有重要意义,并支持在人类临床试验中使用负载抗原的成熟DC。