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Inhibition of CD26 peptidase activity significantly improves engraftment of retrovirally transduced hematopoietic progenitors

Gene Therapy volume 13, pages 652–658 (2006)Cite this article

Abstract

It has previously been shown that inhibition of CD26 (DPPIV/dipeptidylpeptidase IV) peptidase activity improves homing of hematopoietic stem cells (HSCs) to the bone marrow and increases engraftment efficiency. Here, we demonstrate that treatment of retrovirally transduced mouse bone marrow cells with the tri-peptide Diprotin A (Ile-Pro-Ile), a specific inhibitor of CD26, significantly enhances engraftment of retrovirally transduced HSCs. Treatment of transduced bone marrow cells with Diprotin A permitted long-term expression of a retrovirally encoded MHC class I gene on multiple hematopoietic cell lineages after transplantation of a suboptimal number of transduced cells. Secondary transfer experiments revealed that expression of the transduced MHC class I gene resulted from engraftment of transduced HSCs. Expression of the allogeneic MHC class I antigen on bone marrow-derived cells following transplantation of Diprotin A-treated cells was sufficient to induce transplantation tolerance. Therefore, inhibition of CD26 activity significantly enhances engraftment of limited numbers of genetically modified HSCs, resulting in physiologically relevant levels of gene transfer.

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Acknowledgements

The authors wish to thank Drs Mohamed Sayegh and Anil Chandraker for critical review of the manuscript, and members of the Iacomini laboratory for helpful discussions. Jessamyn Bagley is supported in part by a grant from the A-T Children's Project. Daron Forman is supported in part by NIH Training Grant T32 AI07529. This work was supported by Grants R01AI43619-06 and R01AI50602-02 from the National Institutes of Health, and a grant from the American Diabetes Association (7-04-RA-45) to JI.

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  1. Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, MA, USA

    C Tian, J Bagley, D Forman & J Iacomini

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  2. J Bagley
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Correspondence to J Iacomini.

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Tian, C., Bagley, J., Forman, D. et al. Inhibition of CD26 peptidase activity significantly improves engraftment of retrovirally transduced hematopoietic progenitors. Gene Ther 13, 652–658 (2006). https://doi.org/10.1038/sj.gt.3302695

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