Characterization of an Immediate Splenic Precursor of CD8+ Dendritic Cells Capable of Inducing Antiviral T Cell Responses
Characterization of an Immediate Splenic Precursor of CD8+ Dendritic Cells Capable of Inducing Antiviral T Cell Responses
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DOI：
10.4049/jimmunol.0802286
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Segura, Elodie
中科院分区：
文献类型：
--
作者：
Bedoui, Sammy;Prato, Sandro;Segura, Elodie
小鼠脾脏含有三种主要的树突状细胞（DC）群：浆细胞样DC、常规CD 8（+）CD 24（+）DC（CD 8（+）DC）和常规CD 8（-）CD 24（-）DC（CD 8（-）DC）。我们先前已经表明，CD 8（+）DC是体内主要的交叉呈递亚型，并且是抗病毒细胞毒性T淋巴细胞应答的主要诱导剂。在此，我们发现在CD 8（+）DC耗竭后，唯一能够呈递病毒抗原的DC是一个表达CD 24但不表达CD 8的小亚群。这种CD 8（-）CD 24（+）DC群体在用DC生长因子FMS样酪氨酸激酶3配体处理的小鼠中大大扩增。CD 8（-）CD 24（+）DC代表CD 8（+）DC的直接前体，如通过其CD 8（+）DC的特征性标志物的表达模式、其在体外交叉呈递的能力以及其在过继转移到受体小鼠中后转化为CD 8（+）DC所证明的。因此，与终末分化的CD 8（+）DC相比，转移的CD 8（-）CD 24（+）DC在体内的寿命大大增加。此外，在疫苗接种方案中，与CD 8（+）DC相比，CD 8（-）CD 24（+）DC诱导更强的T细胞应答并加速HSV-1的病毒清除。我们的研究结果表明，交叉呈递的能力首先出现在尚未表达CD 8的CD 8（+）DC的直接前体群体中。CD 8（-）CD 24（+）DC在过继转移后诱导免疫应答的增强的能力使其成为基于DC的免疫治疗的有吸引力的新工具。免疫学杂志，2009，182：4200-4207.
Mouse spleens contain three major dendritic cell (DC) populations: plasmacytoid DC, conventional CD8(+)CD24(+) DC (CD8(+) DC), and conventional CD8(-)CD24(-) DC (CD8(-) DC). We have previously shown that CD8(+) DC are the major cross-presenting subtype in vivo and are the main inducers of antiviral cytotoxic T lymphocyte responses. Here we show that after depletion of CD8(+) DC, the only DC capable of viral Ag presentation was a small subset that expresses CD24 but not CD8. This CD8(-)CD24(+) DC population is greatly expanded in mice treated with the DC growth factor FMS-like tyrosine kinase 3 ligand. The CD8(-)CD24(+) DC represent an immediate precursor of CD8(+) DC, as demonstrated by their expression pattern of characteristic markers of CD8(+) DC, their capacity to cross-present in vitro, and their conversion into CD8(+) DC upon adoptive transfer into recipient mice. Accordingly, the lifespan of transferred CD8(-)CD24(+) DC in vivo was greatly enhanced as compared with terminally differentiated CD8(+) DC. Moreover, in a vaccination protocol, CD8(-)CD24(+) DC induced stronger T cell responses and accelerated viral clearance of HSV-1 compared with CD8(+) DC. Our results demonstrate that the ability to cross-present first appears in an immediate precursor population of CD8(+) DC that does not yet express CD8. The enhanced capacity of CD8(-)CD24(+) DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies. The Journal of Immunology, 2009, 182: 4200-4207.