IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells.
IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells.
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DOI：
10.4049/jimmunol.143.8.2514
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发表时间：
1989-10
影响因子：
4.4
通讯作者：
M. Holsti;D. Raulet
中科院分区：
文献类型：
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作者：
M. Holsti;D. Raulet
纯化的T细胞可以在抗TCR单抗和共刺激细胞因子的作用下，被诱导增殖并产生自分泌生长因子IL-2。在以前的一份报告中，我们证明了人IL-6与未溶解的抗TCR Vβ8单抗F23.1一起刺激纯化的T细胞产生IL-2和增殖。在这里，我们显示，当CD4+T细胞被严格纯化到大于99%的CD4+CD8-时，它们只对F23.1和IL-6有微弱的反应。相反，对IL-1有额外的要求，它与IL-6极大地协同作用，诱导长时间(超过7天)的增殖反应和IL-2的产生。用高有丝分裂活性的抗CD3单抗145-2C11代替F23.1也得到了类似的结果。抗IL-2单抗可显著抑制F23.1、IL-1和IL-6诱导的细胞增殖(>80%)，而抗IL-4-mAb不能抑制F23.1、IL-1和IL-6诱导的细胞增殖。根据这一发现，由激活的CD4+细胞组成的条件培养液中含有大量的IL-2，在7天的培养期间，IL-2的含量会增加。这些结果表明，IL-6和IL-1通过诱导自分泌生长因子IL-2的产生来刺激T细胞增殖。此外，两种淋巴因子必须同时存在才能发生激活。文中还讨论了IL-6和IL-1在IL-2基因调控和抗原诱导T细胞活化中的可能作用。
Purified T cells can be induced to proliferate and to produce the autocrine growth factor IL-2 with mAb to the TCR and costimulatory cytokines. In a previous report we demonstrated that human IL-6 stimulates IL-2 production and proliferation of purified T cells, in conjunction with the insolubilized anti-TCR V beta 8 mAb, F23.1. Here we show that when CD4+ T cells are rigorously purified to greater than 99% CD4+CD8-, they respond only weakly to F23.1 and IL-6. Instead, there is an additional requirement for IL-1, which dramatically synergizes with IL-6 to induce prolonged (greater than 7 days) proliferative responses and IL-2 production. Similar results were observed when the highly mitogenic anti-CD3 mAb 145-2C11 was substituted for F23.1. The proliferation induced by F23.1, IL-1, and IL-6 was substantially (greater than 80%) inhibited by a mAb to mouse IL-2, and was not inhibited by an anti-IL-4-mAb. In accordance with this finding, medium conditioned by the activated CD4+ cells contained large amounts of IL-2, which increased over a 7-day culture period. These results demonstrate that IL-6 and IL-1 stimulate T cell proliferation by inducing production of the autocrine growth factor IL-2. In addition, the two lymphokines must be present simultaneously for activation to occur. The possible roles of IL-6 and IL-1 in IL-2 gene regulation and in Ag-induced T cell activation are discussed.