title: SEA antagonizes the imatinib-meditated inhibitory effects on T cell activation via the TCR signaling pathway.
abstract: The BCR-ABL kinase inhibitor imatinib is highly effective in the treatment of chronic myeloid leukemia (CML). However, long-term imatinib treatment induces immunosuppression, which is mainly due to T cell dysfunction. Imatinib can reduce TCR-triggered T cell activation by inhibiting the phosphorylation of tyrosine kinases such as Lck, ZAP70, LAT, and PLC γ 1 early in the TCR signaling pathway. The purpose of this study was to investigate whether the superantigen SEA, a potent T cell stimulator, can block the immunosuppressive effects of imatinib on T cells. Our data show that the exposure of primary human T cells and Jurkat cells to SEA for 24 h leads to the upregulation of the Lck and ZAP70 proteins in a dose-dependent manner. T cells treated with SEA prior to TCR binding had increased the tyrosine phosphorylation of Lck, ZAP70, and PLC γ 1. Pretreatment with SEA prevents the inhibitory effects of imatinib on TCR signaling, which leads to T cell proliferation and IL-2 production. It is conceivable that SEA antagonizes the imatinib-mediated inhibition of T cell activation and proliferation through the TCR signaling pathway.
authors: Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou 510632, China ; Quanzhou Medical college, Quanzhou 362000, China.
authors: Guanming
authors: G
authors: Wang
authors: Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou 510632, China.
authors: Yuhui
authors: Y
authors: Yan
authors: Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou 510632, China.
authors: Xiaohua
authors: X
authors: Chen
authors: Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou 510632, China.
authors: Chen
authors: C
authors: Lin
authors: Institute of Hematology, Medical College, Jinan university, Guangzhou 510632, China ; Key Laboratory for Regenerative Medicine of Ministry of Education, Guangzhou 510632, China.
authors: Yangqiu
authors: Y
authors: Li
mesh_terms: D001549:Benzamides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D000068877:Imatinib Mesylate; D019169:Jurkat Cells; D010766:Phosphorylation; D010879:Piperazines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D011743:Pyrimidines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001549:Benzamides; D004768:Enterotoxins; D010879:Piperazines; D011743:Pyrimidines; D011948:Receptors, Antigen, T-Cell; C026066:enterotoxin A, Staphylococcal; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases