Enhanced activation-induced cell death as a mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity in peripheral T cells
Enhanced activation-induced cell death as a mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity in peripheral T cells
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DOI：
10.1016/s0300-483x(01)00391-2
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发表时间：
2001-08-13
期刊：
影响因子：
4.5
通讯作者：
Nagarkatti, PS
中科院分区：
文献类型：
--
作者：
Camacho, IA;Hassuneh, MR;Nagarkatti, PS
活化后的T细胞经历凋亡，这一过程称为活化诱导的细胞死亡（AICD）。在目前的研究中，我们调查是否2，3，7，8-四氯二苯并-p-二恶英（TCDD）增加AICD，这是否构成TCDD诱导免疫毒性的机制之一。为此，C57 BL 6+ +、C57 BL 6 gld gld（Fas配体缺陷）和C57 BL 6 lpr lpr（Fas缺陷）小鼠用TCDD（50 μ g/kg体重，ip）或载体（玉米油）和抗CD 3 mAb注射到足垫中，3天后，收获腹股沟和腘淋巴结细胞，合并并计数。用抗CD 3 mAb体外培养细胞，并测量细胞增殖。此外，研究了这些细胞在单独使用组织培养基或使用抗CD 3 mAb体外培养时发生细胞凋亡的能力。数据表明，与溶剂处理对照组相比，TCDD处理野生型（+ +）小鼠的淋巴结显示细胞结构减少，T细胞对抗CD 3 mAb的反应性降低。此外，当与来自媒介物处理的小鼠的细胞相比时，来自TCDD处理的小鼠的这种细胞在体外培养时表现出增加的细胞凋亡水平。相比之下，TCDD处理的C57 BL 6 gld gld和C57 BL 6 lpr lpr小鼠的活化淋巴结显示出正常的细胞结构和T细胞对抗CD 3刺激的反应性。此外，与对照组相比，TCDD处理的C57 BL 6 gld gld和C57 BL 6 lpr lpr小鼠的活化淋巴结T细胞未能表现出增加的凋亡。目前的研究表明，TCDD在活化的外周血T细胞中的免疫毒性作用可能是由于通过Fas-Fas配体相互作用介导的AICD增加。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
T cells upon activation undergo apoptosis, a process termed activation-induced cell death (AICD). In the current study, we investigated whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases AICD and whether this constitutes one of the mechanisms by which TCDD induces immunotoxicity. To this end, C57BL 6+ +, C57BL6 gld gld (Fas ligand-defective) and C57BL 6 lpr lpr (Fas-deficient) mice were injected with TCDD (50 mug kg body weight, ip) or the vehicle (corn oil) and with anti-CD3 mAbs into the footpads, 3 days later, inguinal and popliteal lymph node cells were harvested, pooled and enumerated. Cells were cultured in vitro with anti-CD3 mAbs and cell proliferation was measured. Also, such cells were studied for their ability to undergo apoptosis upon in vitro culture with either tissue culture medium alone or with anti-CD3 mAbs. The data demonstrated that lymph nodes from TCDD-treated wild-type (+ +) mice showed a decrease in cellularity and the T cells exhibited decreased responsiveness to anti-CD3 mAbs when compared to the vehicle-treated control group. Furthermore, such cells from TCDD-treated mice exhibited increased levels of apoptosis upon in vitro culture when compared to the cells from vehicle-treated mice. IN contrast, activated lymph nodes from TCDD-treated C57BL 6 gld gld and C57BL 6 lpr lpr mice showed normal cellularity and T cell responsiveness to anti-CD3 stimulation when compared to the vehicle controls. In addition, the activated lymph node T cells from the TCDD-treated C57BL 6 gld gld and C57BL 6 lpr lpr mice failed to exhibit increased apoptosis when compared to the controls. The current study demonstrates that the immunotoxic effects of TCDD in activated peripheral T cells may result from increased AICD mediated through Fas-Fas ligand interactions. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.