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Direct signal transduction via functional interferon-αβ receptors in CD34+ hematopoietic stem cells

Leukemia volume 16, pages 1135–1142 (2002)Cite this article

Abstract

Affinity purified, freshly isolated CD34+ progenitors were shown to express low levels of type I interferon (IFN) receptors (740 ± 60 binding sites/cell, Kd 0.7 ± 0.04 nM) determined by Scatchard's analysis using a radiolabelled, neutralizing, monoclonal antibody directed against the IFNAR1 chain of the human type I IFN receptor. Treatment of freshly isolated (day 0), highly purified (>95% pure) CD34+ cells with recombinant IFN-α resulted in rapid tyrosine phosphorylation and activation of STAT1, Tyk2 and JAK1 as shown by Western immunoblotting. Similarly, IFN treatment was shown by confocal microscopy to result in rapid nuclear localization of the transcription factors IRF1 and STAT2, demonstrating the presence of functional IFN receptors on freshly isolated (day 0) CD34+ cells. The number of specific type I IFN receptor binding sites expressed on hematopoietic progenitor cells increased to some 1440 ± 40 per cell after 11 days of cultivation of CD34+ cells in vitrosuggesting that receptor expression increases with cell differentiation. IFN-mediated signal transduction and the inhibitory effect of IFN-α on 7 or 14 days CFU-GM and BFU-E colony formation was abrogated in the presence of the anti-IFNAR1 mAb, indicating that IFN-α acts directly on the proliferation of human hematopoietic progenitor cells via receptor activated signal transduction without excluding the induction of other cytokines or growth factors by residual accessory cells.

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Acknowledgements

This work was supported by grants from Corixa Inc, and the Association Nouvelles Recherches Biomédicales.

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Authors and Affiliations

  1. Laboratoire d'Oncologie Virale, UPR 9045, CNRS, Villejuif, France

    D Weill, G Bailly, PC Nardeux, MG Tovey & P Eid

  2. Laboratoire d'Hématologie, Hôpital Paul Brousse, Villejuif, France

    S Legras

  3. Inserm U506, Hôpital Paul Brousse, Villejuif, France

    J Giron-Michel & B Azzarone

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Giron-Michel, J., Weill, D., Bailly, G. et al. Direct signal transduction via functional interferon-αβ receptors in CD34+ hematopoietic stem cells. Leukemia 16, 1135–1142 (2002). https://doi.org/10.1038/sj.leu.2402492

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