Hyaluronan Induces Cell Death in Activated T Cells through CD44
Hyaluronan Induces Cell Death in Activated T Cells through CD44
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DOI：
10.4049/jimmunol.181.10.7044
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发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Johnson, Pauline
中科院分区：
文献类型：
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作者：
Ruffell, Brian;Johnson, Pauline
在免疫系统中，白细胞活化诱导CD 44结合透明质酸，一种细胞外基质的成分。在这里，我们使用CD 44的透明质酸结合突变体的获得和损失来检查T细胞中透明质酸结合的结果。用在S180处突变的CD 44转染的Jurkat T细胞（其阻止加入硫酸软骨素）显示组成性高水平的透明质酸结合。这些细胞对活化诱导的细胞死亡更敏感，而表达不能结合透明质酸（R41 A）的CD 44突变体的细胞对细胞死亡具有抗性。在TCR或PMA激活的Jurkat T细胞中，透明质酸诱导快速细胞死亡。这取决于细胞结合透明质酸的水平，以及透明质酸的数量和大小。高分子量的透明质酸具有最大的效果，细胞死亡独立于Fas和半胱天冬酶活化而发生。在脾T细胞中，高透明质酸结合发生在经历活化诱导的细胞死亡的细胞亚群中。此外，透明质酸诱导细胞死亡类似于10%的再活化脾T细胞时，Fas依赖性细胞凋亡被阻止抗体阻断或Fas阴性MRL/lpr T细胞。这表明透明质酸可以通过Fas非依赖性机制诱导活化的高透明质酸结合T细胞中的细胞死亡。免疫学杂志，2008，181：7044-7054.
In the immune system, leukocyte activation induces CD44 to bind hyaluronan, a component of the extracellular matrix. Here we used gain and loss of hyaluronan-binding mutants of CD44 to examine the consequence of hyaluronan binding in T cells. Jurkat T cells transfected with CD44 mutated at S180, which prevented the addition of chondroitin sulfate, displayed constitutively high levels of hyaluronan binding. These cells were more susceptible to activation-induced cell death, whereas cells expressing a CD44 mutant unable to bind hyaluronan (R41A) were resistant to cell death. In TCR or PMA activated Jurkat T cells, hyaluronan induced rapid cell death. This depended on the level of hyaluronan binding by the cell, and the amount and size of hyaluronan. High molecular mass hyaluronan had the greatest effect and cell death occurred independently of Fas and caspase activation. In splenic T cells, high hyaluronan binding occurred in a subpopulation of cells undergoing activation-induced cell death. In addition, hyaluronan induced cell death in similar to 10% of reactivated splenic T cells when Fas-dependent apoptosis was prevented by Ab blocking or in Fas negative MRL/lpr T cells. This demonstrates that hyaluronan can induce cell death in activated, high hyaluronan binding T cells via a Fas-independent mechanism. The Journal of Immunology, 2008, 181: 7044-7054.