Hernández-Caselles T, Martínez-Esparza M, Sancho D, Rubio G, Aparicio P
Department of Biochemistry B and Immunology, School of Medicine, University of Murcia, Spain.
Hum Immunol. 1995 Jul;43(3):181-9. doi: 10.1016/0198-8859(94)00168-p.
We studied the ability of several interleukins to inhibit the cellular death of IL-2-dependent human T cells deprived of IL-2 testing viability, DNA integrity, and expression of bcl-2 gene product. Our in vitro results showed that the addition of IL-7, and in a far less efficient manner IL-4, augmented the viability of IL-2-dependent T-cell clones of different origin, specificity, and phenotype. Furthermore, IL-7 reduced the percentage of apoptotic T cells inhibiting DNA fragmentation. In addition, IL-7 but not IL-4 was consistently able to suppress the cell death of IL-2-dependent T cells triggered by DEX, a synthetic GC. The suppression of T-cell death triggered by IL-7 was not affected by the addition of anti-IL-2 antibody. Interestingly, IL-7 inhibited the downregulation of bcl-2 gene product expression that appeared on TCCs after IL-2 withdrawal and also shared with IL-2 the ability to induce the upregulation of CD25 antigen on activated T lymphocytes in the presence of DEX. These experiments establish a novel role for IL-7 in regulating viability and GC-induced apoptosis on activated human T cells and suggest that the maintenance of bcl-2 levels is a general mechanism by which interleukins preserve activated T cells from undergoing apoptosis.
我们研究了几种白细胞介素抑制白细胞介素-2依赖的人T细胞因缺乏白细胞介素-2而导致细胞死亡的能力，检测了细胞活力、DNA完整性和bcl-2基因产物的表达。我们的体外实验结果表明，添加白细胞介素-7以及效率低得多的白细胞介素-4，可增强不同来源、特异性和表型的白细胞介素-2依赖的T细胞克隆的活力。此外，白细胞介素-7降低了抑制DNA片段化的凋亡T细胞的百分比。另外，白细胞介素-7而非白细胞介素-4能够持续抑制由合成糖皮质激素地塞米松触发的白细胞介素-2依赖的T细胞的死亡。添加抗白细胞介素-2抗体不影响白细胞介素-7触发的T细胞死亡的抑制作用。有趣的是，白细胞介素-7抑制了白细胞介素-2撤除后T细胞克隆上出现的bcl-2基因产物表达的下调，并且在存在地塞米松的情况下，与白细胞介素-2一样具有诱导活化T淋巴细胞上CD25抗原上调的能力。这些实验确立了白细胞介素-7在调节活化的人T细胞的活力和糖皮质激素诱导的凋亡中的新作用，并表明维持bcl-2水平是白细胞介素保护活化T细胞免于凋亡的一般机制。
