Characterization of a common precursor population for dendritic cells

  • A Corrigendum to this article was published on 13 May 2004

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Identification of DC-precursors in mouse peripheral blood.
Figure 2: DC reconstitution by blood DC-precursors.
Figure 3: Links with myeloid and lymphoid lineages and homing potential of DC-precursors.

References

  1. 1

    Banchereau, B. et al. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18, 767–811 (2000).

    CAS  Article  Google Scholar 

  2. 2

    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).

    PubMed  Google Scholar 

  3. 3

    Traver, D. et al. Development of CD8α-positive dendritic cells from a common myeloid progenitor. Science 290, 2152–2154 (2000).

    ADS  CAS  Article  Google Scholar 

  4. 4

    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).

    CAS  Article  Google Scholar 

  5. 5

    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).

    PubMed  Google Scholar 

  6. 6

    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).

    Article  Google Scholar 

  7. 7

    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).

    ADS  Article  Google Scholar 

  8. 8

    Martín, P. et al. Characterization of a new subpopulation of mouse CD8α+ B220+ dendritic cells with tolerogenic potential. Blood (submitted).

  9. 9

    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).

    ADS  CAS  Article  Google Scholar 

  10. 10

    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).

    CAS  Article  Google Scholar 

  11. 11

    Kondo, M., Weissman, I. L. & Akashi, K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661–672 (1997).

    CAS  Article  Google Scholar 

  12. 12

    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).

    CAS  PubMed  Google Scholar 

  13. 13

    Singh, H. Gene targeting reveals a hierarchy of transcription factors regulating specification of lymphoid cell fates. Curr. Opin. Immunol. 8, 160–165 (1996).

    CAS  Article  Google Scholar 

  14. 14

    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).

    CAS  Article  Google Scholar 

  15. 15

    Siegal, F. P. et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 1835–1837 (1999).

    CAS  Article  Google Scholar 

  16. 16

    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).

    CAS  Article  Google Scholar 

  17. 17

    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).

    PubMed  Google Scholar 

  18. 18

    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).

    CAS  PubMed  Google Scholar 

  19. 19

    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).

    CAS  Article  Google Scholar 

  20. 20

    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).

    CAS  Article  Google Scholar 

  21. 21

    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).

    Article  Google Scholar 

Download references

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

Affiliations

Authors

Corresponding author

Correspondence to Carlos Ardavín.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints 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

Download citation

Further reading

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.