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Inactivation of Notch1 in immature thymocytes does not perturb CD4 or CD8 T cell development

Nature Immunology volume 2, pages 235–241 (2001)Cite this article

A Correction to this article was published on 01 May 2001

Abstract

Notch proteins influence cell-fate decisions in many developing systems. Several gain-of-function studies have suggested a critical role for Notch1 signaling in CD4-CD8 lineage commitment, matura-tion and survival in the thymus. However, we show here that tissue-specific inactivation of the gene encoding Notch1 in immature (CD25+CD44−) T cell precursors does not affect subsequent thymocyte development. Neither steady-state numbers nor the rate of production of CD4+ and CD8+ mature thymocytes is perturbed in the absence of Notch1. In addition, Notch1-deficient thymocytes are normally sensitive to spontaneous or glucocorticoid-induced apoptosis. In contrast to earlier re-ports, these data formally exclude an essential role for Notch1 in CD4-CD8 lineage commitment, maturation or survival.

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Figure 1: Tissue specific-targeting of the gene encoding Notch1.
Figure 2: Monitoring CD4-Cre activity with a reporter mouse expressing a floxed H-2Dd (MHC class I) transgene.
Figure 3: Thymocyte subsets of Notch1−/− and control mice.
Figure 4: Absence of Notch1 does not perturb the production rate of mature SP thymocytes.
Figure 5: Normal development of Notch1−/− thymocytes in a competitive situation.
Figure 6: Absence of Notch1 signaling does not affect Bcl-2 or TCRαβ expression or spontaneous or glucocorticoid-induced cell death.
Figure 7: Normal numbers of peripheral T cells in Notch1−/− mice.

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Acknowledgements

We thank C. Maréchal and R. Lees for expert technical assistance. Supported by Swiss Cancer League grant SNSF 31-56075.98 (to A. W.) and by a Swiss National Science Foundation START fellowship (to W. H.)

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Author notes

  1. Talitha Bakker

    Present address: Sir William Dunn School of Pathology, Cellular Immunology Unit, South Parks Road, Oxford, OX1 3RE, UK

Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland

    Anita Wolfer, Talitha Bakker, Anne Wilson, Michael Nicolas, Vassilios Ioannidis, Werner Held, H. Robson MacDonald & Freddy Radtke

  2. Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University Medical Center, New York, 10016, NY, USA

    Dan R. Littman

  3. Departments of Immunology and Pediatrics, University of Washington, Seattle, 98195, WA, USA

    Christopher B. Wilson

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Correspondence to H. Robson MacDonald.

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Wolfer, A., Bakker, T., Wilson, A. et al. Inactivation of Notch1 in immature thymocytes does not perturb CD4 or CD8 T cell development. Nat Immunol 2, 235–241 (2001). https://doi.org/10.1038/85294

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