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Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells

2010; Rockefeller University Press; Volume: 207; Issue: 6 Linguagem: Inglês

10.1084/jem.20092618

1540-9538

Lionel Franz Poulin, Mariolina Salio, Emmanuel Griessinger, Fernando Anjos‐Afonso, Ligia Craciun, Ji‐Li Chen, Anna M. Keller, Olivier Joffre, Santiago Zelenay, Emma Nye, Alaín Le Moine, Florence Faure, Vincent Donckier, David Sancho, Vincenzo Cerundolo, Dominique Bonnet, Caetano Reis e Sousa,

Immune Cell Function and Interaction

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+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8α+ 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.