Bedoui Sammy, Prato Sandro, Mintern Justine, Gebhardt Thomas, Zhan Yifan, Lew Andrew M, Heath William R, Villadangos José A, Segura Elodie
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
J Immunol. 2009 Apr 1;182(7):4200-7. doi: 10.4049/jimmunol.0802286.
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.
小鼠脾脏包含三种主要的树突状细胞（DC）群体：浆细胞样DC、传统的CD8(+)CD24(+) DC（CD8(+) DC）和传统的CD8(-)CD24(-) DC（CD8(-) DC）。我们之前已经表明，CD8(+) DC是体内主要的交叉呈递亚型，并且是抗病毒细胞毒性T淋巴细胞反应的主要诱导者。在此我们表明，在CD8(+) DC耗竭后，唯一能够呈递病毒抗原的DC是一小部分表达CD24但不表达CD8的细胞。在用DC生长因子FMS样酪氨酸激酶3配体处理的小鼠中，这个CD8(-)CD24(+) DC群体大量扩增。CD8(-)CD24(+) DC代表CD8(+) DC的直接前体，这通过它们CD8(+) DC特征性标志物的表达模式、它们在体外交叉呈递的能力以及它们在过继转移到受体小鼠后转化为CD8(+) DC得以证明。因此，与终末分化的CD8(+) DC相比，体内过继转移的CD8(-)CD24(+) DC的寿命大大延长。此外，在一个疫苗接种方案中，与CD8(+) DC相比，CD8(-)CD24(+) DC诱导更强的T细胞反应并加速单纯疱疹病毒1型（HSV-1）的病毒清除。我们的结果表明，交叉呈递能力首先出现在尚未表达CD8的CD8(+) DC的直接前体群体中。CD8(-)CD24(+) DC在过继转移后诱导免疫反应的能力增强，使其成为基于DC的免疫疗法的一种有吸引力的新型工具。
