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Tracing lymphopoiesis with the aid of a pTα-controlled reporter gene

Nature Immunology volume 3, pages 489496 (2002) | Download Citation

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Abstract

A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor α(pTα) promoter, was used to identify lymphoid precursors that expressed pTα intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of lymphocytes but not myeloid cells. The earliest intrathymic precursors were CD4loCD8CD25CD44+c-Kit+ cells that expressed elevated levels of Notch-1 mRNA. Clonogenic assays showed that the extrathymic precursors were common lymphoid progenitors (CLPs) that included CD19, B220+, Thy1+ and CD4+ cells. Thus, the pTα reporter can be used to trace lymphopoiesis between CLPs and αβ T cells. The slower extinction of the hCD25 reporter compared to pTα enabled us to define points at which pTα lineages branched off.

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Acknowledgements

Supported by NIH grants (R01A147281 and R01A145846 to H. v. B.); the “Eugenia Spanopoulou” Irvington Award (to I. A.), the Division of Medical Sciences of the Harvard Medical School (C. M.); and the Cancer Research Institute (B.R.). We thank K. Akashi and P. Kincade for advice and encouragement; A. Harrington for oocyte injections; T. Honjo and Y. Ishida for the hCD25 minigene; and M. Handley and H. Levine for cell sorting. Supported by the Albert J. Ryan Foundation (to C.M.).

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Author notes

    • Fotini Gounari
    • , Iannis Aifantis
    •  & Colin Martin

    These authors contributed equally to this work.

Affiliations

  1. Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

    • Fotini Gounari
    • , Iannis Aifantis
    • , Colin Martin
    • , Sonja Hoeflinger
    •  & Harald von Boehmer
  2. Department of Immunology, Medical Faculty/University Clinics Ulm, D-89070 Ulm, Germany.

    • Hans-Joerg Fehling
  3. Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.

    • Philip Leder
    •  & Boris Reizis

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The authors declare no competing financial interests.

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Correspondence to Harald von Boehmer.

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DOI

https://doi.org/10.1038/ni778