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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1094-1099. Prepublished online as a Blood First Edition Paper on April 20, 2004; DOI 10.1182/blood-2003-12-4266. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4266v1 104/4/1094    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dietz, A. B. Articles by Vuk-Pavlovic, S. Search for Related Content PubMed PubMed Citation Articles by Dietz, A. B. Articles by Vuk-Pavlovic, S. Related Collections Immunobiology Phagocytes Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo Allan B. Dietz, Lina Souan, Gaylord J. Knutson, Peggy A. Bulur, Mark R. Litzow, and Stanimir Vuk-Pavlovi From the Stem Cell Laboratory, Mayo Clinic Cancer Center, Rochester, MN; Division of Hematology, Department of Internal Medicine; Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN. Imatinib mesylate (STI571, imatinib) inhibited DNA synthesis in primary human T cells stimulated with allogeneic mature dendritic cells or phytohemagglutinin (PHA) but did not induce apoptosis. The values for the concentration that inhibits 50% (IC50) of T-cell proliferation stimulated by dendritic cells and PHA were 3.9 µM and 2.9 µM, respectively, that is, within the concentration range found in patients treated with imatinib mesylate. Interestingly, imatinib mesylate did not inhibit expression of T-cell activation markers CD25 and CD69, although it reduced the levels of activated nuclear factor-B (NF-B) and changed phosphorylation or protein levels of Lck, ERK1/2, retinoblastoma protein, and cyclin D3. When T cells were washed free of imatinib mesylate, they proliferated in response to PHA, demonstrating that inhibition is reversible. Treatment with imatinib mesylate led to accumulation of the cells in G0/G1 phase of the cell cycle. The in vitro observations were confirmed in vivo in a murine model of delayed-type hypersensitivity (DTH). In mice treated with imatinib mesylate, DTH was reduced in comparison to sham-injected controls. However, the number of splenic T cells was not reduced showing that, similarly to in vitro observations, imatinib mesylate inhibited T-cell response, but did not cause apoptosis. These findings indicate that long-term administration of high-dose imatinib mesylate might affect immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Imatinib mesylate: a novel immune suppressive agent? Richard T. Maziarz Blood 2004 104: 914-915. [Full Text] [PDF] This article has been cited by other articles: Y. Huang, E. O. Comiskey, R. S. Dupree, S. Li, A. J. Koleske, and J. K. Burkhardt The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse Blood, July 1, 2008; 112(1): 111 - 119. [Abstract] [Full Text] [PDF] M. 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