Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Adult T-cell progenitors retain myeloid potential

Nature volume 452, pages 768–772 (2008)Cite this article

Abstract

During haematopoiesis, pluripotent haematopoietic stem cells are sequentially restricted to give rise to a variety of lineage-committed progenitors. The classical model of haematopoiesis postulates that, in the first step of differentiation, the stem cell generates common myelo-erythroid progenitors and common lymphoid progenitors (CLPs). However, our previous studies in fetal mice showed that myeloid potential persists even as the lineage branches segregate towards T and B cells1,2,3,4,5,6. We therefore proposed the ‘myeloid-based’ model of haematopoiesis7,8, in which the stem cell initially generates common myelo-erythroid progenitors and common myelo-lymphoid progenitors. T-cell and B-cell progenitors subsequently arise from common myelo-lymphoid progenitors through myeloid-T and myeloid-B stages, respectively. However, it has been unclear whether this myeloid-based model is also valid for adult haematopoiesis. Here we provide clonal evidence that the early cell populations in the adult thymus contain progenitors that have lost the potential to generate B cells but retain substantial macrophage potential as well as T-cell, natural killer (NK)-cell and dendritic-cell potential. We also show that such T-cell progenitors can give rise to macrophages in the thymic environment in vivo. Our findings argue against the classical dichotomy model in which T cells are derived from CLPs; instead, they support the validity of the myeloid-based model for both adult and fetal haematopoiesis.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Early progenitors in the adult thymus retain the potential to generate macrophages.
Figure 2: T-cell progenitors in adult thymus that have lost B-cell potential retain macrophage potential.
Figure 3: In vivo evidence that T-cell progenitors contribute to the production of thymic macrophages.
Figure 4: T-cell progenitors retain macrophage potential after B-cell potential has been shut off.

References

  1. Kawamoto, H., Ohmura, K. & Katsura, Y. Direct evidence for the commitment of hematopoietic stem cells to T, B and myeloid lineages in murine fetal liver. Int. Immunol. 9, 1011–1019 (1997)

    Article  CAS  Google Scholar 

  2. Kawamoto, H., Ohmura, K. & Katsura, Y. Presence of progenitors restricted to T, B, or myeloid lineage, but absence of multipotent stem cells, in the murine fetal thymus. J. Immunol. 161, 3799–3802 (1998)

    CAS  PubMed  Google Scholar 

  3. Ohmura, K. et al. Emergence of T, B and myeloid lineage-committed as well as multipotent hematopoietic progenitors in the aorta–gonad–mesonephros region of day 10 fetuses of the mouse. J. Immunol. 163, 4788–4795 (1999)

    CAS  PubMed  Google Scholar 

  4. Kawamoto, H., Ikawa, T., Ohmura, K., Fujimoto, S. & Katsura, Y. T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver. Immunity 12, 441–450 (2000)

    Article  CAS  Google Scholar 

  5. Ikawa, T. et al. Identification of the earliest prethymic T-cell progenitors in murine fetal blood. Blood 103, 530–537 (2004)

    Article  CAS  Google Scholar 

  6. Lu, M., Kawamoto, H., Katsube, Y., Ikawa, T. & Katsura, Y. The common myelolymphoid progenitor: a key intermediate stage in hemopoiesis generating T and B cells. J. Immunol. 169, 3519–3525 (2002)

    Article  CAS  Google Scholar 

  7. Katsura, Y. Redefinition of lymphoid progenitors. Nature Rev. Immunol. 2, 127–132 (2002)

    Article  CAS  Google Scholar 

  8. Kawamoto, H. A close developmental relationship between the lymphoid and myeloid lineages. Trends Immunol. 27, 169–175 (2006)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Kincade, P. W. et al. Nature or nurture? Steady-state lymphocyte formation in adults does not recapitulate ontogeny. Immunol. Rev. 187, 116–125 (2002)

    Article  Google Scholar 

  11. Spangrude, G. J. Divergent models of lymphoid lineage specification: do clonal assays provide all the answers? Immunol. Rev. 187, 40–47 (2002)

    Article  Google Scholar 

  12. Laiosa, C. V., Stadtfeld, M. & Graf, T. Determinants of lymphoid–myeloid lineage diversification. Annu. Rev. Immunol. 24, 705–738 (2006)

    Article  CAS  Google Scholar 

  13. Buza-Vidas, N., Luc, S. & Jacobsen, S. E. Delineation of the earliest lineage commitment steps of haematopoietic stem cells: new developments, controversies and major challenges. Curr. Opin. Hematol. 14, 315–321 (2007)

    Article  Google Scholar 

  14. Lee, C. K. et al. Generation of macrophages from early T progenitors in vitro. J. Immunol. 166, 5964–5969 (2001)

    Article  CAS  Google Scholar 

  15. Balciunaite, G., Ceredig, R. & Rolink, A. G. The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential. Blood 105, 1930–1936 (2005)

    Article  CAS  Google Scholar 

  16. Benz, C. & Bleul, C. C. A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision. J. Exp. Med. 202, 21–31 (2005)

    Article  CAS  Google Scholar 

  17. Nishikawa, S., Ogawa, M., Nishikawa, S., Kunisada, T. & Kodama, H. B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation. Eur. J. Immunol. 18, 1767–1771 (1988)

    Article  CAS  Google Scholar 

  18. Anderson, M. K., Weiss, A. H., Hernandez-Hoyos, G., Dionne, C. J. & Rothenberg, E. V. Constitutive expression of PU.1 in fetal hematopoietic progenitors blocks T cell development at the pro-T cell stage. Immunity 16, 285–296 (2002)

    Article  CAS  Google Scholar 

  19. Masuda, K. et al. Prethymic T-cell development defined by the expression of paired immunoglobulin-like receptors. EMBO J. 24, 4052–4060 (2005)

    Article  CAS  Google Scholar 

  20. Ikawa, M., Yamada, S., Nakanishi, T. & Okabe, M. ‘Green mice’ and their potential usage in biological research. FEBS Lett. 430, 83–87 (1998)

    Article  CAS  Google Scholar 

  21. Ardavin, C., Wu, L., Li, C. L. & Shortman, K. Thymic dendritic cell and T cells develop simultaneously in the thymus from a common precursor population. Nature 362, 761–763 (1993)

    Article  CAS  ADS  Google Scholar 

  22. Lu, M. et al. The earliest thymic progenitors in adults are restricted to T, NK, and dendritic cell lineage and have a potential to form more diverse TCRβ chains than fetal progenitors. J. Immunol. 175, 5848–5856 (2005)

    Article  CAS  Google Scholar 

  23. Wang, B. et al. A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene. Proc. Natl Acad. Sci. USA 91, 9402–9406 (1994)

    Article  CAS  ADS  Google Scholar 

  24. Hollander, G. A. et al. Developmental control point in induction of thymic cortex regulated by a subpopulation of prothymocytes. Nature 373, 350–353 (1995)

    Article  CAS  ADS  Google Scholar 

  25. Surh, C. D. & Sprent, J. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372, 100–103 (1994)

    Article  CAS  ADS  Google Scholar 

  26. Lind, E. F., Prockop, S. E., Porritt, H. E. & Petrie, H. T. Mapping precursor movement through the postnatal thymus reveals specific microenvironments supporting defined stages of early lymphoid development. J. Exp. Med. 194, 127–134 (2001)

    Article  CAS  Google Scholar 

  27. Bell, J. J. & Bhandoola, A. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature doi: 10.1038/nature06840 (this issue)

Download references

Acknowledgements

We thank P. Burrows, W. van Ewijk and W. T. V. Germeraad for critical reading of the manuscript, and O. Kawamoto for valuable advise.

Author Contributions H.W. performed most of experiments, with the assistance of R.S. and K.K. for immunohistochemical analysis and stromal cell co-cultures, respectively. Experiments shown in Fig. 1 and Supplementary Figs 2 and 3 were performed by K.M., and those in Supplementary Fig. 4d by T.I. Y.K. gave critical advice and comments in designing the experiments and writing the paper. H.K. designed the experiments and wrote the paper.

Author information

Author notes

  1. Haruka Wada & Kyoko Masuda

    Present address: Present addresses: Division of Bioregulation Research, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki 216-8512, Japan (H.W.); Institute of Molecular Medicine and Genetics, University of Georgia, GA 30602, USA (K.M.).,

Authors and Affiliations

  1. Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan

    Haruka Wada, Kyoko Masuda, Rumi Satoh, Kiyokazu Kakugawa, Tomokatsu Ikawa, Yoshimoto Katsura & Hiroshi Kawamoto

  2. Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173-8610, Japan

    Yoshimoto Katsura

Authors
  1. Haruka Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoko Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rumi Satoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kiyokazu Kakugawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomokatsu Ikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshimoto Katsura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroshi Kawamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroshi Kawamoto.

Supplementary information

Supplementary information

This file contains Supplementary Figures S1-S8 with Legends and additional references. (PDF 2225 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wada, H., Masuda, K., Satoh, R. et al. Adult T-cell progenitors retain myeloid potential. Nature 452, 768–772 (2008). https://doi.org/10.1038/nature06839

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature06839

This article is cited by

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.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing