Szondy Z
Department of Biochemistry, University Medical School of Debrecen, Hungary.
Immunol Lett. 1997 Jun;58(1):59-65. doi: 10.1016/s0165-2478(97)02713-2.
Both methylprednisolone (MPS) and 2-chloroadenosine (2-CA) were shown previously to induce DNA fragmentation and cell death in human thymocytes at an optimum concentration of 1 and 40 microM, respectively. Though both compounds affected the CD4+CD8+ population, 2-CA depleted primarily thymocytes expressing medium or high levels of CD3-T-cell receptor molecule, while the glucocorticoid treatment affected cells expressing a lower level of CD3-T-cell receptor. Their effect on thymocyte viability and DNA fragmentation was observed already at day 1 of culture and involved the bcl-2 negative thymocytes. Incubation of peripheral T-lymphocytes (which express bcl-2) with the same concentration of MPS did not affect the viability for up to 5 days, while 2-CA induced 100% cell death and DNA fragmentation by day 5. If T-cells were stimulated with concanavalin A in the presence of MPS or 2-CA the cell proliferation was inhibited and a decrease in cell viability with a concomittant increase in DNA fragmentation was observed. If MPS was added at 24 h or later after mitogenic stimulation, it was not able to induce apoptosis and the inhibition of proliferation was less pronounced. 2-CA, on the other hand, inhibited proliferation and induced cell death whenever it was added to the culture. The decreased sensitivity towards the apoptosis induction effects of glucocorticoids at later phases of mitogenic stimulation can not be explained by an increased bcl-2 expression, since its expression level remained constant up to 48 h after mitogenic stimulation. Our data presented in this paper suggest: (1) that T-cells may show different sensitivity towards the same apoptosis inducer signals at different stages of the T-cell development; (2) the apoptotic sensitivity towards various signals may be different at the same stage of T-cell differentiation; and (3) their apoptotic sensitivity does not always correlate with the bcl-2 expression alone.
先前研究表明，甲基强的松龙（MPS）和2-氯腺苷（2-CA）分别在最佳浓度1微摩尔/升和40微摩尔/升时，可诱导人胸腺细胞发生DNA片段化和细胞死亡。尽管这两种化合物都影响CD4+CD8+群体，但2-CA主要使表达中等或高水平CD3-T细胞受体分子的胸腺细胞减少，而糖皮质激素处理则影响表达较低水平CD3-T细胞受体的细胞。在培养第1天就观察到它们对胸腺细胞活力和DNA片段化的影响，且涉及bcl-2阴性的胸腺细胞。用相同浓度的MPS孵育外周T淋巴细胞（表达bcl-2）长达5天，其活力不受影响，而到第5天，2-CA诱导100%细胞死亡和DNA片段化。如果在有MPS或2-CA存在的情况下用伴刀豆球蛋白A刺激T细胞，细胞增殖受到抑制，细胞活力下降，同时DNA片段化增加。如果在有丝分裂原刺激后24小时或更晚添加MPS，则不能诱导细胞凋亡，对增殖的抑制作用也不明显。另一方面，无论何时将2-CA添加到培养物中，它都能抑制增殖并诱导细胞死亡。在有丝分裂原刺激后期对糖皮质激素诱导凋亡作用的敏感性降低，不能用bcl-2表达增加来解释，因为在有丝分裂原刺激后48小时内其表达水平保持恒定。我们在本文中给出的数据表明：（1）T细胞在T细胞发育的不同阶段可能对相同的凋亡诱导信号表现出不同的敏感性；（2）在T细胞分化的同一阶段，对各种信号的凋亡敏感性可能不同；（3）它们的凋亡敏感性并不总是仅与bcl-2表达相关。
