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In mouse, a subset of dendritic cells (DCs) known as CD8alpha+ 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 CD8alpha+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8alpha+ 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 CD8alpha+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8alpha+ DCs) TLR9. DNGR-1+ BDCA3hi DCs 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+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.

Original publication

DOI

10.1084/jem.20092618

Type

Journal article

Journal

J Exp Med

Publication Date

07/06/2010

Volume

207

Pages

1261 - 1271

Keywords

Animals, Antigens, Surface, CD8-Positive T-Lymphocytes, Cross-Priming, Dendritic Cells, Endocytosis, Gene Expression Profiling, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Immunity, Innate, Interleukin-12, Lectins, C-Type, Mice, Phenotype, Poly I-C, Receptors, Mitogen, Spleen, Toll-Like Receptors