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Wang, Yadan, Wu, Xiaofei, Hu, Yu. (1398). Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α. سامانه مدیریت نشریات علمی, 16(4), 278-290. doi: 10.22034/iji.2019.80279
Yadan Wang; Xiaofei Wu; Yu Hu. "Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α". سامانه مدیریت نشریات علمی, 16, 4, 1398, 278-290. doi: 10.22034/iji.2019.80279
Wang, Yadan, Wu, Xiaofei, Hu, Yu. (1398). 'Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α', سامانه مدیریت نشریات علمی, 16(4), pp. 278-290. doi: 10.22034/iji.2019.80279
Wang, Yadan, Wu, Xiaofei, Hu, Yu. Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α. سامانه مدیریت نشریات علمی, 1398; 16(4): 278-290. doi: 10.22034/iji.2019.80279

Multiple Myeloma Bone Marrow Mesenchymal Stromal Cells Inhibit CD8+ T Cell Function in a Process that May Implicate Fibroblast Activation Protein α

Iranian Journal of Immunology
مقاله 2، دوره 16، شماره 4، اسفند 2019، صفحه 278-290    اصل مقاله (557.79 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22034/iji.2019.80279
نویسندگان
Yadan Wang1؛ Xiaofei Wu2؛ Yu Hu* 1
1Department of Hematology, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
2Institute of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
چکیده
Background: Multiple myeloma (MM) is a malignant plasma cell proliferative disorder with limited immunotherapy treatment because of T cell dysfunction. Objective: To investigate the immunomodulatory function of bone marrow mesenchymal stromal cells (MM-BMSCs) on CD8+ T cells. Methods: Proliferation and cytotoxicity were detected by cell counting kit-8 assay. Cell cycle was detected by flow cytometry, and p16 expression was detected by PCR. The expression of fibroblast activation protein α (FAPα) was evaluated by immunohistochemistry. Results: Co-culture of CD8+ T cells with MM-BMSCs decreased the cell survival rate and increased the killing rate (p=0.03, p=0.001, respectively), the percentage of cells in G0/G1 phase and p16 expression (p<0.001). FAPα was mainly in the mesenchymal matrix of the MM microenvironment and elevated in MM derived bone marrow compared to healthy donors (p<0.001). The FAPα inhibitor PT-100, increased survival and the killing rate (p<0.001, p=0.043, respectively), and decreased the percentage of cells in G0/G1 phase and p16 expression (p=0.024, p=0.004, respectively). Conclusion: Therefore, MM-BMSCs inhibit the proliferation and cytotoxicity of CD8+ T cells, significantly block the cell cycle and increase p16 expression in co-cultured CD8+ T cells in a cell-cell contact-dependent manner.
کلیدواژه‌ها
Bone Marrow Mesenchymal Stromal Cells؛ CD8+ T Cell Anergy؛ Fibroblast Activation Protein a؛ Multiple Myeloma
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