Effector γδ T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma
Effector γδ T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma
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DOI：
10.1038/sj.leu.2403693
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发表时间：
2005-04-01
期刊：
影响因子：
11.4
通讯作者：
Massaia, M
中科院分区：
文献类型：
--
作者：
Mariani, S;Muraro, M;Massaia, M
本研究的目的是探讨唑来膦酸 (Zol) 对正常供者和多发性骨髓瘤 (MM) 患者外周血 V gamma 9/V delta 2 (gamma delta) T 细胞的体外免疫调节作用。用 Zol 和低剂量白细胞介素 2 (IL-2) 刺激 γ δ T 细胞，然后分析其增殖、细胞因子的产生以及针对骨髓瘤细胞系和原发性骨髓瘤细胞的效应活性的产生。在 100% 的正常供体和 50% 的 MM 患者中观察到 γδT 细胞增殖。 γ δ T 细胞产生 IFN-γ，表面动员 CD107a 和 CD107b 抗原，并发挥直接的细胞间抗骨髓瘤活性，而与增殖为 Zol 和 IL-2 的能力无关。记忆表型在对 Zol 做出反应而增殖的 MM gamma delta T 细胞（反应者）中占主导地位，而效应细胞在那些不增殖的细胞（无反应者）中占主导地位。 Zol 通过单核细胞依赖性激活 γ δ T 细胞并增强骨髓瘤细胞对 γ δ T 细胞的免疫敏感性来诱导抗骨髓瘤活性。美伐他汀是一种羟甲基戊二酰辅酶A还原酶的特异性抑制剂，完全消除了这种抗骨髓瘤活性。
The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood V gamma 9/V delta 2 (gamma delta) T cells of normal donors and multiple myeloma (MM) patients. gamma delta T cells were stimulated with Zol and low doses of interleukin- 2 (IL-2), and then analyzed for proliferation, cytokine production, and generation of effector activity against myeloma cell lines and primary myeloma cells. Proliferation of gamma delta T cells was observed in 100% of normal donors and 50% of MM patients. gamma delta T cells produced IFN-gamma, surface mobilized the CD107a and CD107b antigens, and exerted direct cell-to-cell antimyeloma activity irrespective of the ability to proliferate to Zol and IL-2. The memory phenotype was predominant in the MM gamma delta T cells that proliferated in response to Zol ( responders), whereas effector cells were predominant in those that did not ( nonresponders). Zol induced antimyeloma activity through the monocyte-dependent activation of gamma delta T cells and by enhancing the immunosensitivity of myeloma cells to gamma delta T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.