Cerdan C, Devilard E, Xerri L, Olive D
National Institute of Health and Medical Research, University of Méditerranée and Department of Hematopathology, Institut Paoli-Calmettes, Marseille, France.
Blood. 2001 Apr 15;97(8):2205-12. doi: 10.1182/blood.v97.8.2205.
Clonal expansion of activated T cells is controlled by homeostatic mechanisms leading to cell death of a large proportion of the cells. The CD3/TcR pathway induces cell death, mostly when triggered in the absence of costimulatory signal. The unique T cell-specific chemokine of the C class, lymphotactin (Lptn), has recently been shown to inhibit the production of Th1-type lymphokines in human CD4(+) T cells. The present study shows the ability of Lptn to costimulate the death of CD4(+) T lymphocytes triggered through CD3/TCR. The Lptn-mediated increased cell death exhibited characteristic features of apoptosis, as mainly determined by DNA fragmentation and exposure of an apoptotic-specific mitochondrial antigen. This apoptosis was dependent on Fas/FasL signaling, was not rescued by addition of interleukin 2, and proceeded with a predominant processing of both initiator procaspase-9 and effector procaspase-7. These caspase activities were further evidenced by specific cleavage of poly(ADP-ribose) polymerase (PARP) and CD3/TCR zeta-chain, but not DNA fragmentation factor (DFF45). This study demonstrates that the functional repertoire of Lptn in the regulation of human CD4(+) T-lymphocyte activation includes the ability to costimulate apoptosis.
活化T细胞的克隆扩增受稳态机制控制，导致大部分细胞死亡。CD3/TcR途径诱导细胞死亡，主要是在缺乏共刺激信号时被触发。C类独特的T细胞特异性趋化因子，淋巴细胞趋化因子（Lptn），最近已被证明能抑制人CD4(+) T细胞中Th1型淋巴因子的产生。本研究显示Lptn具有共刺激通过CD3/TCR触发的CD4(+) T淋巴细胞死亡的能力。Lptn介导的细胞死亡增加表现出凋亡的特征，主要由DNA片段化和凋亡特异性线粒体抗原的暴露所决定。这种凋亡依赖于Fas/FasL信号传导，添加白细胞介素2不能挽救，并且主要伴随着起始半胱天冬酶-9和效应半胱天冬酶-7的加工过程。这些半胱天冬酶活性通过聚（ADP-核糖）聚合酶（PARP）和CD3/TCR ζ链的特异性切割进一步得到证实，但DNA片段化因子（DFF45）未被切割。本研究表明，Lptn在调节人CD4(+) T淋巴细胞活化中的功能谱包括共刺激凋亡的能力。
