Different radiosensitivity of CD4(+)CD25(+) regulatory T cells and effector T cells to low dose gamma irradiation in vitro.
Different radiosensitivity of CD4(+)CD25(+) regulatory T cells and effector T cells to low dose gamma irradiation in vitro.
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DOI：
10.3109/09553002.2010.518208
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发表时间：
2011-01
影响因子：
2.6
通讯作者：
Nelson D
中科院分区：
文献类型：
--
作者：
Cao M;Cabrera R;Xu Y;Liu C;Nelson D
目的：研究人分化簇(CD)4+CD25+调节性T细胞(Treg)和效应T细胞对低剂量伽玛射线的体外辐射敏感性差异，并探讨其机制。采自5名健康人和5名晚期肝细胞癌患者的血样。用磁性微球筛选Treg和CD 4+CD2 5−T细胞。采用[~3H]-胸腺嘧啶核苷掺入法、Luminex比色法和流式细胞术比较了不同剂量−-射线对Treg和CD_4+CD_(25)γT细胞的增殖、细胞因子分泌和凋亡相关蛋白表达的影响。在Treg和CD_4+CD_(25)−T细胞中存在剂量依赖性的增殖抑制，这种抑制与诱导细胞凋亡的作用是平行的。Treg细胞对低剂量辐射(0.94Gray[Gy])比效应T细胞更敏感。干扰素-γ(干扰素γ)显著上调，白细胞介素10(IL-10)显著下调。晚期肝细胞癌患者外周血对低剂量伽玛射线的免疫应答增强。与CD_4+CD_(25)−T细胞相比，T细胞表达活化的半胱氨酸天冬氨酸蛋白酶-3、CD95、B细胞淋巴瘤2(Bc l-2)相关X蛋白(BAX)。此外，伽玛射线还能激活CD_4+CD_(25)−T细胞表达CD_(25)。这些研究表明，Treg细胞比CD_4+CD_(25)−T细胞对低剂量辐射更敏感。与CD_4+CD_(25)−T细胞相比，Treg细胞中caspase-3、CD_(95)和Bax等凋亡相关蛋白的表达明显增加。我们的结果表明，低剂量的伽玛射线治疗可能是增强晚期肝癌患者免疫反应的可行策略。
To determine the radiosensitivity difference of human Cluster of Differentiation (CD)4+CD25+ regulatory T cells (Treg) and effector T cells to low dose gamma ray and elucidate the underlying mechanisms in vitro. Blood samples were collected from five health subjects and five patients with advanced hepatocellular carcinoma (HCC). Treg and CD4+CD25− T cells were selected using magnetic microbeads. The proliferative profiles, cytokine secretion, and differential expressions of apoptosis-related proteins in Treg and CD4+CD25− T cells were compared using [3H]-thymidine incorporation, Luminex assay and flow cytometry when treated with various low doses of γ-ray. A dose-dependent reduction of proliferation in response to irradiation which paralleled the induction of apoptosis existed in Treg and CD4+CD25− T cells. Treg were more radiosensitive to low-dose irradiation (0.94 Gray [Gy]) than effector T cells. The interferon-γ (IFNγ) was significantly upregulated and interleukin 10 (IL-10) was significantly downregulated in irradiated Treg. An enhanced immune response to low dose gamma ray existed in the peripheral blood in patients with advanced HCC. Higher levels of active caspase-3, CD95, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression were observed in Treg compared to CD4+CD25− T cells. In addition, gamma irradiation activated CD4+CD25−T cells to express CD25. These studies revealed that Treg were more radiosensitive than CD4+CD25− T cells to low dose irradiation. Higher expressions of apoptosis-related proteins such as caspase-3, CD95 and Bax were observed in Treg when compared to CD4+CD25− T cells. Our results suggest that treatment with low doses of gamma irradiation may be a viable strategy to enhance immune response in patients with advanced HCC.
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影响因子：
2.5
作者：
Liu, Shu-Zheng
通讯作者：
Liu, Shu-Zheng
影响因子：
5.5
作者：
DUNN, PL;NORTH, RJ
通讯作者：
NORTH, RJ
影响因子：
7.5
作者：
Finkel, T
通讯作者：
Finkel, T
影响因子：
9.7
作者：
Jung, MY;Kang, HJ;Moon, A
通讯作者：
Moon, A
影响因子：
3.4
作者：
Kipnis, J;Avidan, H;Schwartz, M
通讯作者：
Schwartz, M