Article thumbnail

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

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

Abstract

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

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2882845
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2008). Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells
  2. (1992). CD1b restricts the response of human CD4-8- T lymphocytes to a microbial antigen.
  3. (2010). CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells.
  4. (2000). CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal.
  5. (2008). CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells.
  6. (2004). Cell Mol.
  7. (1995). CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes.
  8. (2007). Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells.
  9. (2005). Cutting edge: generation of splenic CD8+ and CD8- dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures.
  10. (1998). Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs.
  11. (2008). Dendritic cells in vivo: a key target for a new vaccine science.
  12. (1995). Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products.
  13. (2005). Development and activation of human dendritic cells in vivo in a xenograft model of human hematopoiesis.
  14. (2007). Differential antigen processing by dendritic cell subsets in vivo.
  15. (1996). Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified.
  16. (2008). Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells.
  17. (2002). ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8+ dendritic cells.
  18. (2006). Identification and expression of mouse Langerin (CD207) in dendritic cells.
  19. (2000). Identification of NY-ESO-1 peptide analogues capable of improved stimulation of tumor-reactive CTL.
  20. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.
  21. (2000). Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells.
  22. kinetic basis for heightened immunogenicity of T cell vaccines.
  23. (2009). Long-lasting cross-presentation of tumor antigen in
  24. (2008). Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule.
  25. (2010). Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8+ conventional dendritic cells.
  26. (2003). Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation.
  27. (2010). Quantitative proteomics reveals subset-specific viral recognition in dendritic cells.
  28. (2004). Species-specific recognition of single-stranded RNA via toll-like receptor
  29. (2002). The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo.
  30. (2006). The number and distribution of blood dendritic cells in the epidermis and dermis of healthy human subjects. Folia Histochem.
  31. (2009). The origin and development of nonlymphoid tissue CD103+ DCs.
  32. (2003). Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 + DC correlates with unresponsiveness to imidazoquinolines.