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

Tian, C, Bagley, J, Forman, D, Iacomini, J·2006·Gene Therapy
DOI 10.1038/sj.gt.3302695
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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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Cited by

Metadata

Authors
Tian, C., Bagley, J., Forman, D., & Iacomini, J.
Venue
Gene Therapy
Publisher
Springer Science and Business Media LLC
Published
2005-12-08
Volume
13
Issue
7
Pages
652-658
ISSN
  • 0969-7128
  • 1476-5462
DOI
10.1038/sj.gt.3302695
Cited by
30
References
0
Language
en
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