Van Damme J, Uyttenhove C, Houssiau F, Put W, Proost P, Van Snick J
Rega Institute for Medical Research, University of Leuven, Belgium.
Eur J Immunol. 1992 Nov;22(11):2801-8. doi: 10.1002/eji.1830221108.
Two mouse helper T cell clones that proliferate in response to murine interleukin (IL)-9 could also be grown in conditioned medium of stimulated human connective tissue cells. The activity was not due to known T cell growth factors including human IL-9, which is not effective on mouse cells. This growth-stimulatory activity for TS1 cells (GATS) was co-induced with IL-6 on normal fibroblasts and certain sarcoma cell lines stimulated with IL-1, double-stranded RNA, virus or phorbol ester. However, the conditions for optimal induction and the kinetics of production were found to be different for IL-6 and GATS. GATS from phorbol ester-stimulated human hepatosarcoma cells co-purified with IL-6, but could be separated from it by subsequent cation-exchange fast-protein liquid chromatography and reverse-phase high-performance liquid chromatography. Homogeneous tumor cell-derived GATS was a 25-kDa protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas IL-6 produced by these cells appeared in its 23-kDa form. Pure GATS was found to be inactive in the B cell hybridoma growth assay for IL-6. Finally, GATS was identified by NH2-terminal sequence analysis of the mature protein as leukemia inhibitory factor or human interleukin for DA cells (LIF/HILDA). The effect of LIF/HILDA on T cells was not mediated by IL-2, IL-4 or IL-9 production. Since this cytokine has not previously been reported to act on T cells, further investigation of its role in T cell activation should be taken into consideration.
两种可对小鼠白细胞介素（IL）-9产生增殖反应的小鼠辅助性T细胞克隆，也能够在受刺激的人结缔组织细胞的条件培养基中生长。该活性并非由包括人IL-9在内的已知T细胞生长因子所致，因为人IL-9对小鼠细胞无效。这种对TS1细胞的生长刺激活性（GATS）与IL-6在经IL-1、双链RNA、病毒或佛波酯刺激的正常成纤维细胞和某些肉瘤细胞系上共同诱导产生。然而，发现IL-6和GATS的最佳诱导条件和产生动力学有所不同。来自佛波酯刺激的人肝癌细胞的GATS与IL-6共同纯化，但随后可通过阳离子交换快速蛋白质液相色谱和反相高效液相色谱将其与IL-6分离。在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳上，均一的肿瘤细胞衍生的GATS是一种25 kDa的蛋白质，而这些细胞产生的IL-6则以其23 kDa的形式出现。发现纯GATS在针对IL-6的B细胞杂交瘤生长测定中无活性。最后，通过对成熟蛋白的NH2末端序列分析，将GATS鉴定为白血病抑制因子或DA细胞的人白细胞介素（LIF/HILDA）。LIF/HILDA对T细胞的作用不是由IL-2、IL-4或IL-9的产生介导的。由于此前尚未报道这种细胞因子作用于T细胞，因此应考虑进一步研究其在T细胞活化中的作用。
