Espevik T, Figari I S, Ranges G E, Palladino M A
Department of Molecular Biology and Immunology, Genentech, Inc., South San Francisco, CA 94080.
J Immunol. 1988 Apr 1;140(7):2312-6.
We have investigated the ability of porcine-platelet-derived transforming growth factor-beta 1 (TGF-beta 1) to inhibit the generation of lymphokine-activated killer (LAK) cells by human rIL-2. The results demonstrate that TGF-beta 1, in a dose-related manner, significantly inhibits rIL-2-induced LAK cell activity against Daudi and COLO target cells and, to a lesser degree, against K-562 cells. Maximal inhibition was obtained by the addition of TGF-beta 1 at the time of culture initiation and, to a lesser degree, on day 1. Only minimal inhibition was obtained when TGF-beta 1 addition was delayed until day 2 of culture or when added directly into the LAK cell assay. Additional studies demonstrated that porcine platelet-derived TGF-beta 2 and human rTGF-beta 1 inhibited LAK cell generation similar to that obtained with TGF-beta 1. The inhibition of LAK cell activity by TGF-beta 1 was reversed by the addition of human rTNF-alpha at the initiation of culture. In addition, rTNF-alpha synergized with suboptimal levels of rIL-2 in the generation of LAK activity. After stimulation with rIL-2, LAK cells produced significant levels of IFN-gamma, TNF-alpha, and TNF-beta. TGF-beta 1 inhibited the production of these cytokines in a dose-related manner. The results extend the previous known activities for human rTNF-alpha and TGF-beta 1 and further demonstrate the reciprocal relationship between these two molecules in the regulation of certain immune functions.
我们研究了猪血小板衍生的转化生长因子-β1（TGF-β1）抑制人重组白细胞介素-2（rIL-2）诱导的淋巴因子激活的杀伤（LAK）细胞生成的能力。结果表明，TGF-β1以剂量相关的方式显著抑制rIL-2诱导的针对Daudi和COLO靶细胞的LAK细胞活性，对K-562细胞的抑制作用较小。在培养开始时添加TGF-β1可获得最大抑制效果，在第1天添加的抑制效果稍差。当TGF-β1的添加延迟至培养第2天或直接添加到LAK细胞测定中时，仅获得最小抑制效果。进一步的研究表明，猪血小板衍生的TGF-β2和人重组TGF-β1对LAK细胞生成的抑制作用与TGF-β1相似。在培养开始时添加人重组肿瘤坏死因子-α（rTNF-α）可逆转TGF-β1对LAK细胞活性的抑制作用。此外，rTNF-α在LAK活性生成中与次优水平的rIL-2协同作用。经rIL-2刺激后，LAK细胞产生大量的干扰素-γ、肿瘤坏死因子-α和肿瘤坏死因子-β。TGF-β1以剂量相关的方式抑制这些细胞因子的产生。这些结果扩展了先前已知的人rTNF-α和TGF-β1的活性，并进一步证明了这两种分子在某些免疫功能调节中的相互关系。
