Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells
摘要：
In mouse, a subset of dendritic cells (DCs) known as CD8α+DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8α+DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8α+DCs in phenotype and function. We describe the presence of such cells in the spleens of humans and humanized mice and report on a protocol to generate them in vitro. Like mouse CD8α+DCs, human DNGR-1+BDCA3hiDCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8α+DCs) TLR9. DNGR-1+BDCA3hiDCs respond to poly I:C and agonists of TLR8, but not of TLR7, and produce interleukin (IL)-12 when given innate and T cell–derived signals. Notably, DNGR-1+BDCA3+DCs from in vitro cultures efficiently internalize material from dead cells and can cross-present exogenous antigens to CD8+T cells upon treatment with poly I:C. The characterization of human DNGR-1+BDCA3hiDCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.
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关键词：
Animals Humans Mice Spleen Dendritic Cells CD8-Positive T-Lymphocytes Hematopoietic Stem Cells Poly I-C Lectins, C-Type Receptors, Mitogen
DOI：
10.1084/jem.20092618
被引量：
年份：
2010
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掌桥科研
万方医学
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