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Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation
Clinical & Experimental Immunology ( IF 4.6 ) Pub Date : 2021-07-31 , DOI: 10.1111/cei.13650
Shonia Subramaniam 1, 2 , Jeya Seela Anandha Rao 3 , Premdass Ramdas 4 , Mei Han Ng 5 , Methil Kannan Kutty 6 , Kanga Rani Selvaduray 2 , Ammu Kutty Radhakrishnan 3, 7
Affiliation  

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (Treg) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p < 0.05), CD8+ (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed Treg cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-γ and lower transforming growth factor (TGF)-ꞵ levels were noted in the γT3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-12ꞵ2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the γT3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4+ T cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T cell-dependent cell-mediated immune responses and suppressed T cells in the tumour microenvironment in a syngeneic mouse model of breast cancer.

中文翻译:

每天补充γ-生育三烯酚的小鼠肿瘤中调节性T细胞浸润减少

γ-生育三烯酚 (γT3) 是维生素 E 的类似物,对免疫系统具有有益作用,包括免疫调节特性。本研究报告了在乳腺癌同基因小鼠模型中,每日补充 γT3 对宿主 T 辅助细胞 (Th) 和 T 调节细胞 (T reg ) 群的免疫调节作用。在接种同基因 4T1 小鼠乳腺癌细胞(4T1 细胞)之前,雌性 BALB/c 小鼠通过口服管饲法喂食 γT3 或载体(大豆油)2 周。补充持续到小鼠被安乐死。小鼠 ( n = 6) 在特定时间点实施安乐死以进行各种分析(血液白细胞、细胞因子产生和免疫组织化学)。每7天测量一次肿瘤体积。对从脾培养物中分离的肿瘤特异性 T 淋巴细胞进行基因表达研究。补充 γT3 可增加 CD4 + ( p  < 0.05)、CD8 + ( p  < 0.05) T 细胞和自然杀伤细胞 ( p  < 0.05) 但抑制 T reg细胞 ( p < 0.05) 与用载体喂养的动物相比,在外周血中。在 γT3 喂养的小鼠中观察到较高的干扰素 (IFN)-γ 和较低的转化生长因子 (TGF)-ꞵ 水平。免疫组织化学结果显示,CD4 +细胞浸润增加,白细胞介素 12 受体-β2 (IL-12ꞵ2R)、白细胞介素 (IL)-24 的表达增加,以及表达叉头盒 P3 (FoxP3) 的细胞表达减少。 γT3 喂养的动物。基因表达研究表明,从喂食 γT3 的小鼠中分离出的脾 CD4 + T 细胞中七个显着基因的下调。在同基因的乳腺癌小鼠模型中补充来自棕榈油的 γT3 诱导的 T 细胞依赖性细胞介导的免疫反应并抑制肿瘤微环境中的 T 细胞。
更新日期:2021-07-31
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