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- W1990751781 abstract "RATIONALE: Imatinib mesylate (IM) is a tyrosine kinase inhibitor that inhibits the BCR-ABL oncogene and is an effective therapy for BCR-ABL (+) leukemias. IM is the first successful targeted therapy for chronic myelogenous leukemia (CML). Recent reports demonstrated that IM inhibited proliferation of normal T cells, but its effect on cytokine synthesis by T cells is not known. METHODS: CD3+ T cells were isolated from 10 normal subjects by magnetic bead separation technique. The CD3+ T cells were untreated or pretreated with 5 μM IM for 30 min and then activated through the TCR with immobilized anti-CD3 and soluble anti-CD28, and the cultures incubated at 37 °C for up to 96h. At 8h, 16h, 24h, 48h, 72h, and 96h into the incubation period, aliquots of culture supernatant were harvested and assayed for Th1 (IL-2, IFN-γ, IL-15) and Th2 (IL-4, IL-5, IL-10) cytokines by Luminex Multiplex Bead Array assay. RESULTS: Culture supernatants of T cells that were pretreated with IM and subsequently activated through the TCR with anti-CD3 and anti-CD28 produced significantly lower levels of IL-2, IFN-γ, IL-5, and IL-10 at 24h, 48h, 72h, and 96h post activation than cultures that were not pretreated with IM (all points had p < 0.05). CONCLUSIONS: Downregulation of cytokine synthesis by IM-treated normal T cells corroborated published data that IM suppressed the phosphorylation of lck and ERK1/2, both associated with TCR-mediated signaling in activated T cells. Further investigation is needed to determine the clinical relevance of cytokine modulation in patients receiving IM." @default.
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- W1990751781 date "2005-02-01" @default.
- W1990751781 modified "2023-09-27" @default.
- W1990751781 title "Imatinib mesylate (Gleevec, STI-571) suppresses cytokine production by normal T-cells activated through T-cell receptor (TCR) signaling" @default.
- W1990751781 doi "https://doi.org/10.1016/j.jaci.2004.12.893" @default.
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