Induction of competence and progression signals in human T lymphocytes by phorbol esters and calcium ionophores.
Induction of competence and progression signals in human T lymphocytes by phorbol esters and calcium ionophores.
复制标题
通过佛波酯和钙离子载体诱导人 T 淋巴细胞的能力和进展信号。
DOI：
10.1002/jcp.1041370217
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发表时间：
1988
影响因子：
5.6
通讯作者：
Gelfand,EW
中科院分区：
文献类型：
--
作者：
Kumagai,N;Benedict,SH;Mills,GB;Gelfand,EW
我们研究了磷脂酯和钙离子载体对人T淋巴细胞增殖能力（IL - 2反应性）的诱导和进展。佛博尔酯、佛博尔12,13 -二丁酸酯（PDB）和钙离子载体离子霉素诱导的增殖程度取决于暴露于这些物质的时间，达到最大增殖需要超过6小时。在短暂暴露于这两种试剂30分钟后，没有引起显著的增殖，T细胞对外源性白细胞介素2 （IL‐2）产生增殖反应。在没有离子霉素的情况下，这些能态T细胞也在PDB孵育后进展到DNA合成。EGTA阻断了PDB或IL - 2对增殖能力的诱导，表明跨膜Ca2+通量在这一阶段是强制性的。由于其他酚酯和合成的二酰基甘油也刺激了受感细胞中的DNA合成，因此很可能是由蛋白激酶c的激活引发了这一进程。在短暂暴露于PDB和离子霉素后，随后与PDB孵育诱导基因表达和IL - 2的分泌，并增强了IL - 2受体在受感细胞中的表达。因此，我们已经证明，Ca2+动员是使T细胞能够表达功能性IL - 2受体，在随后的PDB孵育中产生IL - 2所必需的，并且蛋白激酶C的持续激活似乎是IL - 2产生和随后的胜任T细胞向DNA合成的进展所必需的。
We have investigated the induction of competence (IL‐2 responsiveness) and progression in human T lymphocyte proliferation triggered by phorbol ester and calcium ionophore. The degree of proliferation induced with the phorbol ester, phorbol 12,13‐dibutyrate (PDB) and the calcium ionophore ionomycin was dependent on the duration of exposure to these agents, with more than 6 h required for obtaining maximum proliferation. Following brief exposure to both agents for 30 min, which did not cause significant proliferation, T cells became competent to proliferate in response to exogenous interleukin 2 (IL‐2). These competent T cells also progressed to DNA synthesis following incubation with PDB in the absence of ionomycin. Induction of competence to proliferate in response to either PDB or IL‐2 was blocked by EGTA, suggesting that transmembrane Ca2+flux was obligatory at this stage. Since other phorbol esters and synthetic diacylglycerols also stimulated DNA synthesis in competent cells, it is likely that progression was triggered by activation of protein kinase C. Following a brief exposure to PDB and ionomycin, subsequent incubation with PDB induced gene expression and secretion of IL‐2 and augmented the expression of IL‐2 receptors in the competent cells. Thus, we have demonstrated that Ca2+mobilization is required for rendering T cells competent to express functional IL‐2 receptors, to produce IL‐2 in response to subsequent incubation with PDB, and that sustained activation of protein kinase C seems necessary for IL‐2 production and subsequent progression of competent T cells to DNA synthesis.