The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells
The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells
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DOI：
10.1007/s00011-012-0567-y
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发表时间：
2013-02-01
影响因子：
6.7
通讯作者：
Lumniczky, Katalin
中科院分区：
文献类型：
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作者：
Balogh, Andrea;Persa, Eszter;Lumniczky, Katalin
放射治疗会影响抗肿瘤免疫反应;因此，研究放射对免疫系统各个部分的影响非常重要。本文报道了C57 Bl/6小鼠经2戈伊照射后，不同时间点脾淋巴细胞亚群的变化，结果表明：照射后总CD 4+细胞数的下降幅度大于CD 4 + Foxp 3 + T细胞数的下降幅度。T细胞比CD 4 + Foxp 3- T细胞更不易于辐射诱导的凋亡。在增殖的CD 4+池中的CD 4 + Foxp 3-和CD 4 + Foxp 3+部分的比例从对照动物的74：26逐渐变化到照射后11天的59：41，表明Treg池的增殖和再生的更动态的增加。表达细胞表面CTLA 4（一种与Treg细胞活化相关的抗原）的CD 4 + Foxp 3+级分从未照射小鼠中的5.3%增加至照射后三天的10.5%。IL-10 mRNA的表达适度上调，而TGF-β的表达不受影响。另一方面，辐射使Treg抑制效应T细胞增殖的能力降低了2.5倍，Treg比CD 4 + Foxp 3-细胞更具辐射抗性，更不易于辐射诱导的凋亡，并且具有更快的再增殖动力学，但是辐射的Treg在功能上受到损害，具有降低的抑制能力。
Radiotherapy affects antitumor immune responses; therefore, it is important to study radiation effects on various compartments of the immune system. Here we report radiation effects on the homeostasis and function of regulatory T (Treg) cells, which are important in down-regulating antitumor immune responses.C57Bl/6 mice were irradiated with 2 Gy and alterations in splenic lymphocyte fractions analyzed at different intervals.Total CD4+ numbers showed stronger decrease after irradiation than CD4+Foxp3+ Tregs. Tregs were less prone to radiation-induced apoptosis than CD4+Foxp3- T cells. The ratio of CD4+Foxp3- and CD4+Foxp3+ fractions within the proliferating CD4+ pool progressively changed from 74:26 in control animals to 59:41 eleven days after irradiation, demonstrating a more dynamic increase in the proliferation and regeneration of the Treg pool. The CD4+Foxp3+ fraction expressing cell-surface CTLA4, an antigen associated with Treg cell activation increased from 5.3 % in unirradiated mice to 10.5 % three days after irradiation. The expression of IL-10 mRNA was moderately upregulated, while TGF-beta expression was not affected. On the other hand, irradiation reduced Treg capacity to suppress effector T cell proliferation by 2.5-fold.Tregs are more radioresistant, less prone to radiation-induced apoptosis, and have faster repopulation kinetics than CD4+Foxp3- cells, but irradiated Tregs are functionally compromised, having a reduced suppressive capacity.