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The cytotoxic molecule granulysin is capable of inducing either chemotaxis or fugetaxis in dendritic cells depending on maturation: a role for Vδ2+ γδ T cells in the modulation of immune response to tumour?
Immunology ( IF 4.9 ) Pub Date : 2020-08-13 , DOI: 10.1111/imm.13248 Emma L Sparrow 1, 2 , Daniel W Fowler 1 , Joe Fenn 1 , Jonathan Caron 1 , John Copier 1 , Angus G Dalgleish 1 , Mark D Bodman-Smith 1
Immunology ( IF 4.9 ) Pub Date : 2020-08-13 , DOI: 10.1111/imm.13248 Emma L Sparrow 1, 2 , Daniel W Fowler 1 , Joe Fenn 1 , Jonathan Caron 1 , John Copier 1 , Angus G Dalgleish 1 , Mark D Bodman-Smith 1
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Release of granulysin by γδ T cells contributes to tumour cell killing. A cytolytic 9000 MW isoform of granulysin kills tumour cells directly, whereas a 15 000 MW precursor has been hypothesized to cause both the maturation and migration of dendritic cell (DC) populations. Recruiting DC to a tumour is beneficial as these cells initiate adaptive immune responses, which contribute to the eradication of malignancies. In this study, Vδ2+ γδ T cells were activated by stimulation of peripheral blood mononuclear cells with zoledronic acid or Bacillus Calmette–Guérin (BCG), or were isolated and cultured with tumour targets. Although a large proportion of resting Vδ2+ γδ T cells expressed 15 000 MW granulysin, 9000 MW granulysin expression was induced only after stimulation with BCG. Increased levels of activation and granulysin secretion were also observed when Vδ2+ γδ T cells were cultured with the human B‐cell lymphoma line Daudi. High concentrations of recombinant 15 000 MW granulysin caused migration and maturation of immature DC, and also initiated fugetaxis in mature DC. Conversely, low concentrations of recombinant 15 000 MW granulysin resulted in migration of mature DC, but not immature DC. Our data therefore support the hypothesis that Vδ2+ γδ T cells can release granulysin, which may modulate recruitment of DC, initiating adaptive immune responses.
中文翻译：
具有细胞毒性的颗粒溶素可以根据成熟程度诱导树突状细胞趋化性或泛函性：Vδ2+γδT细胞在调节对肿瘤的免疫反应中的作用？
γδT细胞释放颗粒溶素有助于杀死肿瘤细胞。颗粒溶素的细胞溶解9000兆瓦同工型可直接杀死肿瘤细胞，而据推测有15000兆瓦的前体可引起树突状细胞（DC）群体的成熟和迁移。向肿瘤招募DC是有益的，因为这些细胞启动了适应性免疫应答，这有助于根除恶性肿瘤。在这项研究中，V δ 2个+ γδ T细胞由外周血单核细胞用唑来膦酸或卡介苗（BCG）的刺激而活化，或者被分离并与肿瘤靶培养。虽然静止V的大比例δ 2 + γδT细胞表达15000 MW颗粒溶素，仅在BCG刺激后才诱导9000 MW颗粒溶素表达。当V，也观察到活化和颗粒溶分泌水平的增加δ 2个+ γδ T细胞与人类B细胞淋巴瘤系的Daudi进行培养。高浓度的重组15000 MW颗粒溶素引起未成熟DC的迁移和成熟，也引发了成熟DC中的功能分解。相反，低浓度的重组15000 MW颗粒溶素导致成熟DC迁移，但未成熟DC迁移。因此，我们的数据支持了V中的假设δ 2个+ γδ T细胞可以释放颗粒溶素，其可调节DC的募集，启动适应性免疫应答。
更新日期：2020-10-22
中文翻译：
具有细胞毒性的颗粒溶素可以根据成熟程度诱导树突状细胞趋化性或泛函性：Vδ2+γδT细胞在调节对肿瘤的免疫反应中的作用？
γδT细胞释放颗粒溶素有助于杀死肿瘤细胞。颗粒溶素的细胞溶解9000兆瓦同工型可直接杀死肿瘤细胞，而据推测有15000兆瓦的前体可引起树突状细胞（DC）群体的成熟和迁移。向肿瘤招募DC是有益的，因为这些细胞启动了适应性免疫应答，这有助于根除恶性肿瘤。在这项研究中，V δ 2个+ γδ T细胞由外周血单核细胞用唑来膦酸或卡介苗（BCG）的刺激而活化，或者被分离并与肿瘤靶培养。虽然静止V的大比例δ 2 + γδT细胞表达15000 MW颗粒溶素，仅在BCG刺激后才诱导9000 MW颗粒溶素表达。当V，也观察到活化和颗粒溶分泌水平的增加δ 2个+ γδ T细胞与人类B细胞淋巴瘤系的Daudi进行培养。高浓度的重组15000 MW颗粒溶素引起未成熟DC的迁移和成熟，也引发了成熟DC中的功能分解。相反，低浓度的重组15000 MW颗粒溶素导致成熟DC迁移，但未成熟DC迁移。因此，我们的数据支持了V中的假设δ 2个+ γδ T细胞可以释放颗粒溶素，其可调节DC的募集，启动适应性免疫应答。
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