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Thymopoiesis independent of common lymphoid progenitors

Nature Immunology volume 4, pages 168–174 (2003)Cite this article

Abstract

Early T lineage progenitors (ETPs) in the thymus are thought to develop from common lymphoid progenitors (CLPs) in the bone marrow (BM). We compared thymic ETPs to BM CLPs in mice and found that they differed in several respects. Thymic ETPs were not interleukin 7 (IL-7)–responsive and generated B lineage progeny with delayed kinetics, whereas BM CLPs were IL-7–responsive and rapidly generated B cells. ETPs sustained production of T lineage progeny for longer periods of time than BM CLPs. Analysis of Ikaros-deficient mice that exhibit ongoing thymopoiesis without B lymphopoeisis revealed near-normal frequencies of thymic ETPs, yet undetectable numbers of BM CLPs. We conclude that ETPs can develop via a CLP-independent pathway.

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Figure 1: Definition of the earliest thymic progenitors within the CD44+CD25− (DN1) compartment.
Figure 2: Cytokine responsiveness and surface phenotype of precursor populations.
Figure 3: B lineage production kinetics of defined precursor populations.
Figure 4: T lineage production kinetics of defined precursor populations.
Figure 5: Ikaros−/− mice contain ETPs but lack detectable BM CLPs.
Figure 6: D-J rearrangement status of IgH and TCRβ in precursor populations.

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Acknowledgements

We thank K. Georgopoulos for Ikaros−/− mice and helpful discussions and W. Pear, M. Cancro and T. Laufer for reviewing this manuscript. We thank D. Fonseca for help with DNA sequencing and W. DeMuth, K. Rudd and R. C. Lindsley for expert technical assistance. We gratefully acknowledge the expert technical support in flow cytometry provided by the Abramson Cancer Center Flow Cytometry and Cell Sorting Shared Resource and in particular the efforts of R. Schretzenmair and H. Pletcher. Supported by NIH grants AI52861, AG20818 and AI053284 (to D.A.) and grant number IRG-78-002-25 from the American Cancer Society as well as grants from the Concern Foundation and the McCabe Fund (to A.B.).

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  1. Sungjune Kim

    Present address: Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104-6160, PA, USA

    David Allman, Arivazhagan Sambandam, Sungjune Kim, Juli P. Miller, David Well, Anita Meraz & Avinash Bhandoola

  2. Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104-6160, PA, USA

    David Allman & Juli P. Miller

  3. Haverford College, Haverford, 19041, PA, USA

    Antonio Pagan

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Allman, D., Sambandam, A., Kim, S. et al. Thymopoiesis independent of common lymphoid progenitors. Nat Immunol 4, 168–174 (2003). https://doi.org/10.1038/ni878

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