Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells.

Journal article

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.

Authors: Poulin, L; Salio, M; Griessinger, E; Anjos-Afonso, F; Craciun, L

• Publication status: Published
• Journal: Journal of experimental medicine
• Volume: 207
• Issue: 6
• Pages: 1261-1271
• Publication date: 2010-06-01
• DOI: 10.1084/jem.20092618
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Poly I-C; Gene Expression Profiling; Interleukin-12; Lectins, C-Type; Gene Expression Regulation; Toll-Like Receptors; Immunity, Innate; Dendritic Cells; Spleen; Animals; Hematopoietic Stem Cells; Endocytosis; Phenotype; Mice; Humans; Antigens, Surface; CD8-Positive T-Lymphocytes; Receptors, Mitogen; Cross-Priming