Ferlazzo V, Sferrazza C, Caccamo N, Di Fede G, Di Lorenzo G, D'Asaro M, Meraviglia S, Dieli F, Rini G, Salerno A
Dept. of Biopathology and Biomedical Methods, University of Palermo, 90134 Palermo, Italy.
Int J Immunopathol Pharmacol. 2006 Apr-Jun;19(2):309-17. doi: 10.1177/039463200601900208.
In this study we have evaluated the in vitro effects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on Vgamma9Vdelta2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of Vgamma9Vdelta2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of Vgamma9Vdelta2 T cell subsets, with decrease of T(naive) and T(CM) cells and increase of T(EM) and T(EMRA) Vgamma9Vdelta2cells, indicating that in vitro treatment with aminobisphosphonates induces Vgamma9Vdelta2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, Vgamma9Vdelta2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-gamma and acquired the ability to kill tumor target cells.
在本研究中,我们评估了四种不同的氨基双膦酸盐(阿仑膦酸盐、利塞膦酸盐、奈立膦酸盐和唑来膦酸盐)对Vγ9Vδ2 T细胞活化和分化的体外作用。所有测试的氨基双膦酸盐均可在健康供体的原代外周血单核细胞(PBMC)培养物中诱导Vγ9Vδ2 T淋巴细胞的IL-2依赖性活化和扩增。最值得注意的是,它们还决定了Vγ9Vδ2 T细胞亚群的不同分布,T(幼稚)细胞和T(中央记忆)细胞减少,而T(效应记忆)和T(终末分化记忆)Vγ9Vδ2细胞增加,这表明用氨基双膦酸盐进行体外处理可诱导Vγ9Vδ2 T淋巴细胞向效应/细胞毒性表型分化。因此,用氨基双膦酸盐和IL-2培养的Vγ9Vδ2 T淋巴细胞显示出较高的γ干扰素含量,并获得了杀伤肿瘤靶细胞的能力。