IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients
IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients
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DOI：
10.1182/blood-2005-06-2399
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发表时间：
2006-03-15
期刊：
影响因子：
20.3
通讯作者：
Rosenberg, ST
中科院分区：
文献类型：
--
作者：
Ahmadzadeh, M;Rosenberg, ST
白细胞介素-2（IL-2）在历史上被称为T细胞生长因子。来自基因敲除小鼠的累积证据表明，IL-2对体内CD 4（+）CD 25（+）调节性T细胞的稳态和功能至关重要。然而，尚未在啮齿动物或人类中研究在免疫完整宿主中施用IL-2的影响。在这里，我们研究了IL-2给药对免疫完整的黑色素瘤或肾癌患者中人CD 4 + CD 2 Ehi T细胞的频率和功能的影响。我们发现IL-2处理后CD 4（+）CD 25（hi）T细胞的频率显著增加，并且这些细胞表达与调节性T细胞相关的表型标记。此外，在IL-2处理后，CD 4 T细胞中Foxp 3（一种仅在调节性T细胞上表达的转录因子）的转录物和蛋白质水平均持续增加。对增加的CD 4（+）CD 25（hi）T细胞数量的功能分析显示，该群体在体外表现出有效的抑制活性。总的来说，我们的研究结果表明，高剂量IL-2的施用增加了循环中CD 4（+）CD 25（hi）Foxp 3（+）调节性T细胞的频率。我们的研究结果表明，选择性抑制IL-2介导的调节性T细胞的增强可能会提高IL-2给药的治疗效果。
Interleukin-2 (IL-2) is historically known as a T-cell growth factor. Accumulating evidence from knockout mice suggests that IL-2 is crucial for the homeostasis and function of CD4(+)CD25(+) regulatory T cells in vivo. However, the impact of administered IL-2 in an immune intact host has not been studied in rodents or humans. Here, we studied the impact of IL-2 administration on the frequency and function of human CD4+CD2Ehi T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4(+)CD25(hi) T cells was significantly increased after IL-2 treatment, and these cells expressed phenotypic markers associated with regulatory T cells. In addition, both transcript and protein levels of Foxp3, a transcription factor exclusively expressed on regulatory T cells, were consistently increased in CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4(+)CD25(hi) T cells revealed that this population exhibited potent suppressive activity in vitro. Collectively, our results demonstrate that administration of high-dose IL-2 increased the frequency of circulating CD4(+)CD25(hi) Foxp3(+) regulatory T cells. Our findings suggest that selective inhibition of IL-2-mediated enhancement of regulatory T cells may improve the therapeutic effectiveness of IL-2 administration.