Imatinib impairs the proliferation and function of CD4+CD25+ regulatory T cells in a dose-dependent manner

  • Authors:
    • Jinfei Chen
    • Anita Schmitt
    • Krzysztof Giannopoulos
    • Baoan Chen
    • Markus Rojewski
    • Hartmut Döhner
    • Donald Bunjes
    • Michael Schmitt
  • View Affiliations

  • Published online on: November 1, 2007     https://doi.org/10.3892/ijo.31.5.1133
  • Pages: 1133-1139
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Abstract

The tyrosine kinase inhibitor imatinib has been reported to inhibit CD8+ T lymphocytes. Little is known about its effects on CD4+CD25+ regulatory T cells (Treg cells) which might regulate the graft-vs.-leukemia (GVL) reaction after allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusion (DLI). This is of particular interest in patients with relapse of chronic myeloid leukemia (CML) after allo-SCT, as the two therapeutical options DLI and imatinib might interact reversely. Here, we demonstrate that the proliferation of CD4+CD25+ Treg cells and their production of IL-10, TGF-β1 and granzyme B as markers of activation were significantly down-regulated by imatinib in a dose-dependent manner. In addition, the expression of surface CD69, both surface and intracellular GITR, FoxP3, CD152 (CTLA) of activated CD4+CD25+ Treg cells were inhibited by imatinib in a dose-dependent manner. In light of these findings, clinical administration of imatinib might not result in a reduction of the GVL effect on CML patients receiving imatinib after allo-SCT and/or DLI or other CD8+ T lymphocyte based immunotherapies as the function of CD8+ cytotoxic T lymphocytes and CD4+CD25hi Treg cells is hampered in a similar way by imatinib.

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November 2007
Volume 31 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Chen, J., Schmitt, A., Giannopoulos, K., Chen, B., Rojewski, M., Döhner, H. ... Schmitt, M. (2007). Imatinib impairs the proliferation and function of CD4+CD25+ regulatory T cells in a dose-dependent manner. International Journal of Oncology, 31, 1133-1139. https://doi.org/10.3892/ijo.31.5.1133
MLA
Chen, J., Schmitt, A., Giannopoulos, K., Chen, B., Rojewski, M., Döhner, H., Bunjes, D., Schmitt, M."Imatinib impairs the proliferation and function of CD4+CD25+ regulatory T cells in a dose-dependent manner". International Journal of Oncology 31.5 (2007): 1133-1139.
Chicago
Chen, J., Schmitt, A., Giannopoulos, K., Chen, B., Rojewski, M., Döhner, H., Bunjes, D., Schmitt, M."Imatinib impairs the proliferation and function of CD4+CD25+ regulatory T cells in a dose-dependent manner". International Journal of Oncology 31, no. 5 (2007): 1133-1139. https://doi.org/10.3892/ijo.31.5.1133