Abstract
Dendritic cells (DCs) are essential for the establishment of immune responses against pathogens and tumour cells, and thus have great potential as tools for vaccination and cancer immunotherapy trials. Experimental evidence has led to a dual DC differentiation model, which involves the existence of both myeloid- and lymphoid-derived DCs1. But this concept has been challenged by recent reports demonstrating that both CD8- and CD8+ DCs, considered in mice as archetypes of myeloid and lymphoid DCs respectively, can be generated from either lymphoid2,3,4 or myeloid progenitors3,4. The issue of DC physiological derivation therefore remains an open question. Here we report the characterization of a DC-committed precursor population, which has the capacity to generate all the DC subpopulations present in mouse lymphoid organs—including CD8- and CD8+ DCs, as well as the B220+ DC subset—but which is devoid of myeloid or lymphoid differentiation potential. These data support an alternative model of DC development, in which there is an independent, common DC differentiation pathway.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Banchereau, B. et al. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811 (2000).
Martín, P. et al. Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8α- and CD8α+ dendritic cells are generated from CD4low lymphoid–committed precursors. Blood 96, 2511–2519 (2000).
Traver, D. et al. Development of CD8α-positive dendritic cells from a common myeloid progenitor. Science 290, 2152–2154 (2000).
Manz, M. G., Traver, D., Miyamoto, T., Weissman, I. L. & Akashi, K. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97, 3333–3341 (2001).
Anjuère, F. et al. Definition of dendritic cell subpopulations present in the spleen, Peyer's patches, lymph nodes and skin of the mouse. Blood 93, 590–598 (1999).
Martínez del Hoyo, G., Martín, P., Fernández Arias, C., Rodríguez-Marín, A. & Ardavín, C. CD8α+ dendritic cells originate from the CD8α- dendritic cell subset by a maturation process involving CD8α, DEC-205 and CD24 upregulation. Blood 99, 999–1004 (2002).
Ardavín, C., Wu, L., Li, C. L. & Shortman, K. Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. Nature 362, 761–763 (1993).
Martín, P. et al. Characterization of a new subpopulation of mouse CD8α+ B220+ dendritic cells with tolerogenic potential. Blood (submitted).
Akashi, K., Traver, D., Miyamoto, T. & Weissman, I. L. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404, 193–197 (2000).
Mebius, R. E. et al. The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3- cells, as well as macrophages. J. Immunol. 166, 6593–6601 (2001).
Kondo, M., Weissman, I. L. & Akashi, K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661–672 (1997).
Lyman, S. D. & Jacobsen, S. E. W. c-kit ligand and flt3 ligand: Stem/progenitor cell factors with overlapping yet distinct activities. Blood 91, 1101–1134 (1998).
Singh, H. Gene targeting reveals a hierarchy of transcription factors regulating specification of lymphoid cell fates. Curr. Opin. Immunol. 8, 160–165 (1996).
Mojica, M. P. et al. Phenotypic distinction and functional characterization of pro-B cells in adult mouse bone marrow. J. Immunol. 166, 3042–3051 (2001).
Siegal, F. P. et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 1835–1837 (1999).
Cella, M. et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nature Med. 5, 919–923 (1999).
Ardavín, C. et al. B cell response after MMTV infection: extrafollicular plasmablasts represent the main infected population and can transmit viral infection. J. Immunol. 162, 2538–2545 (1999).
Sozzani, S. et al. Cutting edge: Differential regulation of chemokine receptors during dendritic cell maturation: A model for their trafficking properties. J. Immunol. 161, 1083–1086 (1998).
Tudor, K.-S. R. S., Payne, K. J., Yamashita, Y. & Kincade, P. W. Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events. Immunity 12, 335–345 (2000).
Rolink, A. et al. A subpopulation of B220+ cells in murine bone marrow does not express CD19 and contains natural killer cell progenitors. J. Exp. Med. 183, 187–194 (1996).
Anjuère, F., Martínez del Hoyo, G., Martín, P. & Ardavín, C. Langerhans cells acquire a CD8+ dendritic cell phenotype on maturation by CD40 ligation. J. Leukocyte Biol. 67, 206–209 (2000).
Acknowledgements
This work was supported by the European Commission, Comunidad de Madrid and Ministerio de Ciencia y Tecnología of Spain. We thank A. Rolink for the anti-CD40 hybridoma FGK45, K. Akashi for advice on SCL detection, G. Márquez for CCR6 and CCR7 primers, D.F. Tough for IFNα primer sequences, D. Kolakofsky for Sendai virus, H. Acha-Orbea for MMTV, and A. Rodríguez-Marín and V. Parrillas for discussions.
Author information
Authors and Affiliations
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Rights and permissions
About this article
Cite this article
del Hoyo, G., Martín, P., Vargas, H. et al. Characterization of a common precursor population for dendritic cells. Nature 415, 1043–1047 (2002). https://doi.org/10.1038/4151043a
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/4151043a
This article is cited by
-
Biosafety Level 3 setup for multiphoton microscopy in vivo
Scientific Reports (2017)
-
Continuous retinoic acid induces the differentiation of mature regulatory monocytes but fails to induce regulatory dendritic cells
BMC Immunology (2014)
-
The Bloodline of CD8α+ Dendritic Cells
Molecules and Cells (2012)
-
Enemy at the gates: dendritic cells and immunity to mucosal pathogens
Cell Research (2010)
-
Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination
Cancer Immunology, Immunotherapy (2010)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.