Both Langerhans cells and interstitial DC cross-present melanoma antigens and efficiently activate antigen-specific CTL
Both Langerhans cells and interstitial DC cross-present melanoma antigens and efficiently activate antigen-specific CTL
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DOI：
10.1002/eji.200636499
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发表时间：
2007-09-01
影响因子：
5.4
通讯作者：
Banchereau, Jacques
中科院分区：
文献类型：
--
作者：
Cao, Tinghua;Ueno, Hideki;Banchereau, Jacques
树突状细胞（DC）具有向CD 8（+）T细胞呈递外部抗原的独特能力，即交叉呈递。然而，目前还没有完全确定交叉呈递的能力是否仅限于人类DC的一个独特子集。在这里，我们表明，两个主要的髓样DC亚群，即朗格汉斯细胞（LC）和间质DC（Int-DC），有能力在体外交叉呈递抗原的CD 8 + T细胞。LC和Int-DC获自通过用GM-CSF、FLT 3-L和TNF-α培养人CD 34（+）-造血祖细胞产生的DC（CD 34-DC）。两种DC亚群都能够捕获坏死/凋亡的同种异体黑色素瘤细胞并将抗原呈递给CD 8（+）T细胞，从而有效地将初始CD 8（+）T细胞引发为能够杀死黑色素瘤细胞的CTL。引人注目的是，用负载坏死/凋亡黑色素瘤细胞的亚群（LC或Int-DC）或总CD 34-DC单次刺激足以激活从转移性黑色素瘤患者获得的黑色素瘤特异性记忆CD 8（+）T细胞，使其成为有效的CTL。因此，本研究提供了在临床试验中使用载有坏死/凋亡同种异体黑色素瘤细胞的CD 34-DC的基本原理。
Dendritic cells (DC) have a unique capacity to present external antigens to CD8(+) T cells , i.e. cross-presentation. However, it is not fully established whether the ability to cross-presentation is restricted to a unique subset of DC in humans. Here, we show that two major myeloid DC subsets, i.e. Langerhans cells (LC) and interstitial DC (Int-DC), have the ability to cross-present antigens to CD8+ T cells in vitro. LC and Int-DC were obtained from DC generated by culturing human CD34(+)-hematopoietic progenitor cells with GM-CSF, FLT3-L, and TNF-alpha (CD34-DC). Both DC subsets were able to capture necrotic/apoptotic allogeneic melanoma cells and present antigens to CD8(+) T cells, resulting in efficient priming of naive CD8(+) T cells into CTL capable of killing melanoma cells. Strikingly, a single stimulation with either subset (LC or Int-DC) or total CD34-DC loaded with necrotic/apoptotic melanoma cells was sufficient to activate melanoma-specific memory CD8(+) T cells obtained from patients with metastatic melanoma to become effective CTL. Thus, this study provides the rationale to use CD34-DC loaded with necrotic/apoptotic allogeneic melanoma cells in a clinical trial.