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Retroviral transduction of IL-7Rα into IL-7Rα−/− bone marrow progenitors: correction of lymphoid deficiency and induction of neutrophilia

Gene Therapy volume 12, pages 1761–1768 (2005)Cite this article

Abstract

Defects in the gene for the IL-7 receptor (R) α chain are one cause of severe combined immunodeficiency disease (SCID) based on a strict requirement for IL-7 in T lymphoid development and survival. We tested the feasibility and potentially undesirable consequences of IL-7Rα gene transfer as a therapy for this genetic defect. The murine IL-7Rα gene was introduced into IL-7Rα−/− bone marrow progenitors using retrovirus and transplanted into Rag−/− recipient mice. Both αβ and γδ T cells were reconstituted in thymus and spleen showing proof of principle. B-cell development was also restored in some mice, but their numbers were much lower than in the T-cell compartment. Splenomegaly was observed due to an increase in neutrophils. We showed that hematopoeitic progenitors, after transfection with IL-7Rα, could respond to IL-7 in vitro by a striking production of neutrophils and other myeloid cells. These data indicate that although IL-7 is a critical lymphopoietin, ectopic expression of its receptor on multipotential progenitors can also induce production of myeloid cells, presumably through survival and proliferation signals that are not restricted to lymphoid cells. This supports the stochastic model of progenitor differentiation, in which cytokines give permissive and not instructive signals.

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Acknowledgements

We thank R Wyles for technical assistance, K Noer for flow cytometry and J Oppenheim for comments on the manuscript.

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Authors and Affiliations

  1. Laboratory of Molecular Regulation, National Cancer Instutute, NIH, Frederick, MD, USA

    Q Jiang, W-Q Li, K D Klarmann & S K Durum

  2. SAIC, Frederick, MD, USA

    F B Aiello & J R Keller

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  1. Q Jiang
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  2. W-Q Li
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  3. F B Aiello
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Jiang, Q., Li, WQ., Aiello, F. et al. Retroviral transduction of IL-7Rα into IL-7Rα−/− bone marrow progenitors: correction of lymphoid deficiency and induction of neutrophilia. Gene Ther 12, 1761–1768 (2005). https://doi.org/10.1038/sj.gt.3302558

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  • DOI: https://doi.org/10.1038/sj.gt.3302558

Keywords

  • IL-7
  • IL-7R
  • severe combined immunodeficiency
  • neutrophilia

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