Imatinib impairs the proliferation and function of CD4+CD25+ regulatory T cells in a dose-dependent manner.
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 (T(reg) 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+ T(reg) cells and their production of IL-10, TGF-beta1 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+ T(reg) 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+CD25(hi) Treg cells is hampered in a similar way by imatinib.
Chen
Jinfei
J
Department of Internal Medicine III, University Clinic, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.
Schmitt
Anita
A
Giannopoulos
Krzysztof
K
Chen
Baoan
B
Rojewski
Markus
M
Döhner
Hartmut
H
Bunjes
Donald
D
Schmitt
Michael
M
D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D000068877:Imatinib Mesylate; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000970:Antineoplastic Agents; D001549:Benzamides; D060908:CTLA-4 Antigen; D016207:Cytokines; D051858:Forkhead Transcription Factors; D000068877:Imatinib Mesylate; D037181:Lectins, C-Type; D010879:Piperazines; D011743:Pyrimidines; D000099192:CD69 Antigens; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human