Saiagh S, Auger C, Fabien N, Monier J C
Laboratoire d'Immunologie, Faculté de Médecine A. Carrel, Lyon, France.
Immunopharmacol Immunotoxicol. 1994 Nov;16(4):553-76. doi: 10.3109/08923979409019739.
The effect of cyclosporin A (CsA) on mouse thymocytes was investigated in vitro. Ultrastructural examination and DNA electrophoresis of 24hr-CsA-treated thymocytes showed chromatin condensation, cellular shrinkage and nuclear fragmentation in oligonucleosomal fragments. DNA labeling of CsA-treated-thymocytes with propidium iodide (PI) showed an increase in the number of apoptotic nuclei compared to untreated thymocytes. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific to particular thymocyte subsets showed that CsA induces a decrease in the relative number of immature double positive (DP) CD4+CD8+ thymocytes in direct proportion to the concentration of CsA. No significant changes were observed in mature single positive (SP) CD4+CD8- and CD8+CD4- cells. Moreover, the cell viability of CsA-treated thymocytes was decreased. These results suggest that CsA induces the programmed cell death of thymocytes in vitro. Taken together with our previous study on the in vivo effect of CsA on mouse thymus and thymocytes, the present study confirms that, in addition to its effect on the thymic epithelium, CsA acts directly on thymocytes by inducing their programmed cell death. We postulate that immature DP thymocytes are the most likely targets of CsA.
在体外研究了环孢菌素A（CsA）对小鼠胸腺细胞的作用。对经CsA处理24小时的胸腺细胞进行超微结构检查和DNA电泳，结果显示染色质凝聚、细胞皱缩以及寡核小体片段中的核碎片化。用碘化丙啶（PI）对经CsA处理的胸腺细胞进行DNA标记，结果显示与未处理的胸腺细胞相比，凋亡细胞核的数量增加。此外，使用针对特定胸腺细胞亚群的单克隆抗体（mAb）进行流式细胞术分析表明，CsA诱导未成熟双阳性（DP）CD4⁺CD8⁺胸腺细胞的相对数量减少，且与CsA的浓度成正比。在成熟单阳性（SP）CD4⁺CD8⁻和CD8⁺CD4⁻细胞中未观察到显著变化。此外，经CsA处理的胸腺细胞的细胞活力降低。这些结果表明，CsA在体外诱导胸腺细胞的程序性细胞死亡。结合我们之前关于CsA对小鼠胸腺和胸腺细胞体内作用的研究，本研究证实，除了对胸腺上皮的作用外，CsA还通过诱导胸腺细胞的程序性细胞死亡直接作用于胸腺细胞。我们推测未成熟的DP胸腺细胞最有可能是CsA的靶标。
