活化的 CD4+T 细胞通过干扰素-γ和 TNF-α的协同作用增强辐射效应。

Activated CD4+ T cells enhance radiation effect through the cooperation of interferon-gamma and TNF-alpha.

机构信息

Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama 36604-1405, USA.

出版信息

BMC Cancer. 2010 Feb 23;10:60. doi: 10.1186/1471-2407-10-60.

DOI:10.1186/1471-2407-10-60

PMID:20178622

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2843673/

Abstract

BACKGROUND

Approaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.

METHODS

CD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed gamma-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.

RESULTS

Presensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4+ T cells were primarily responsible for the observed effect. IFN-gamma seemed to play a major role. TNF-alpha, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-gamma. aCD4S, but not IFN-gamma or IFN-gamma/TNF-alpha combination, was found to enhance the gamma-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by gamma-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.

CONCLUSIONS

Our findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.

摘要

背景

增强辐射效应的方法可能会改善临床结果并降低毒性。在这里，我们研究了激活的 CD4+T 细胞（aCD4）是否可以作为有效的放射增敏剂。

方法

用抗 CD3 和抗 CD28 mAb 激活 CD4+T 细胞。将 Hela 细胞用 aCD4 或条件培养基（aCD4S）或重组细胞因子预先敏化 2 天，然后进行γ射线照射。将处理过的细胞再培养 2 到 5 天，进行细胞增殖、细胞周期和 Western blot 分析。为了验证，还使用了其他癌细胞系。

结果

用 aCD4 预先敏化肿瘤细胞可显著抑制肿瘤细胞生长。从激活的 CD4+T 细胞分泌的可溶性因子是观察到的效应的主要原因。IFN-γ似乎起主要作用。TNF-α本身无活性，但可显著增强 IFN-γ的放射增敏作用。发现 aCD4S 而非 IFN-γ或 IFN-γ/TNF-α 组合可增强γ射线照射诱导的 G2/M 期阻滞。用 aCD4S 预先敏化 Hela 细胞后，Bax 表达明显上调，然后进行γ射线照射。aCD4 的放射增敏活性不仅在 Hela 细胞系中观察到，而且在各种组织学的其他癌细胞系中也观察到。