The small heat shock protein 27 is a key regulator of CD8+ CD57+ lymphocyte survival.

The small heat shock protein 27 is a key regulator of CD8+ CD57+ lymphocyte survival.
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DOI:
10.4049/jimmunol.0902953
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发表时间:
2010-05-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Doseff AI
Doseff AI
中科院分区:
其他
文献类型:
--
作者:
Wood KL;Voss OH;Huang Q;Parihar A;Mehta N;Batra S;Doseff AI

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CD 8 + CD 57 −和CD 8 + CD 57+淋巴细胞寿命的差异已被记录。较低的数量和较短的寿命是正常个体中CD 8 + CD 57+的特征。然而,CD 8 + CD 57+在某些疾病状态中扩增,包括T细胞大颗粒白血病和其他血液恶性肿瘤。导致CD 8 + CD 57 −和CD 8 + CD 57+寿命差异的机制仍然难以捉摸。在这项研究中,我们证明了小热休克蛋白(Hsp)27是CD 8 + CD 57+淋巴细胞寿命的关键调节因子。我们发现Hsp 27在CD 8 + CD 57+淋巴细胞中的表达显著低于CD 8 + CD 57 −淋巴细胞。相反,Hsp 60和Hsp 70以相当的水平表达。与其他抗凋亡Bcl-2样分子不同,Hsp 27的表达与CD 8 + CD 57+和CD 8 + CD 57 −寿命密切相关。我们证明,在CD 8 + CD 57+淋巴细胞中Hsp 27过表达到CD 8 + CD 57 −淋巴细胞中正常水平可减少细胞凋亡。因此,沉默CD 8 + CD 57 −淋巴细胞中的Hsp 27会增加细胞凋亡。总的来说,这些结果表明,热休克蛋白27是一个关键的调节正常的CD 8 + CD 57+寿命支持其作为一个标志物的寿命在这个谱系,并提出了一种机制,负责减少细胞凋亡和克隆扩增的某些疾病状态的特点。
Differences in CD8+CD57− and CD8+CD57+ lymphocyte lifespan have been documented. Lower numbers and shorter lifespan are characteristic of CD8+CD57+ in normal individuals. However, CD8+CD57+ are expanded in certain disease states including T cell large granular leukemia and other hematologic malignancies. The mechanisms responsible for the differences in CD8+CD57− and CD8+CD57+ lifespan remain elusive. In this study, we demonstrate that the small heat shock protein (Hsp) 27 is a key regulator of CD8+CD57+ lymphocyte lifespan. We found that Hsp27 expression is significantly lower in CD8+CD57+ than in CD8+CD57− lymphocytes. In contrast, Hsp60 and Hsp70 are expressed at comparable levels. Unlike other antiapoptotic Bcl-2–like molecules, the expression of Hsp27 tightly correlates with CD8+CD57+ and CD8+CD57−lifespan. We demonstrate that Hsp27 overexpression in CD8+CD57+ lymphocytes to levels found normally in CD8+CD57− lymphocytes decreased apoptosis. Accordingly, silencing of Hsp27 in CD8+CD57− lymphocytes increased apoptosis. Collectively these results demonstrate that Hsp27 is a critical regulator of normal CD8+CD57+ lifespan supporting its use as a marker of lifespan in this lineage, and suggest a mechanism responsible for the decreased apoptosis and clonal expansion characteristic of certain disease states.
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发表时间: 2001-02-01
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