Ayroldi E, Sorci G, Cannarile L, Riccardi C
Institute of Pharmacology, University of Perugia, Italy.
Nat Immun. 1992 Mar-Apr;11(2):92-104.
We investigated the possible role of tumor necrosis factor-alpha (TNF-alpha) in the interleukin-2 (IL-2)-dependent generation of natural killer (NK) cells from bone marrow precursors. TNF-alpha synergistically augmented both cytotoxic activity against NK-sensitive targets and cell number at the end of the 7-day incubation period. After this time, NK activity was not induced by TNF-alpha in the absence of IL-2. The cytotoxic cells generated by IL-2 + TNF-alpha had the phenotype of mature NK cells, including expression of NK-1.1, asialo-GM1, Ly-5, LFA-1 and Thy-1. TNF-alpha was also able to up-regulate the mRNA expression for the IL-2 receptor alpha-chain (P55) as well as the mRNA expression of c-myc protooncogene. Blocking studies with monoclonal antibodies against the alpha-chain P55 of the IL-2 receptor confirmed the functional role ascribed to IL-2 in the in vitro generation of NK cells from bone marrow cultures. Additional proliferation studies demonstrated that the up-regulation of c-myc protooncogene was associated with an increased uptake of thymidine. These data indicate that the TNF-alpha-induced increase of IL-2-dependent NK cell generation from bone marrow precursors was associated with an augmented proliferation and an up-regulation of mRNA expression for IL-2 receptor and c-myc protooncogene.
我们研究了肿瘤坏死因子-α（TNF-α）在骨髓前体细胞依赖白细胞介素-2（IL-2）生成自然杀伤（NK）细胞过程中可能发挥的作用。在7天培养期结束时，TNF-α协同增强了对NK敏感靶标的细胞毒性活性以及细胞数量。在此之后，在没有IL-2的情况下，TNF-α不会诱导NK活性。由IL-2 + TNF-α产生的细胞毒性细胞具有成熟NK细胞的表型，包括NK-1.1、去唾液酸GM1、Ly-5、淋巴细胞功能相关抗原-1（LFA-1）和Thy-1的表达。TNF-α还能够上调IL-2受体α链（P55）的mRNA表达以及c-myc原癌基因的mRNA表达。用抗IL-2受体α链P55的单克隆抗体进行的阻断研究证实了IL-2在骨髓培养物体外生成NK细胞中所起的功能作用。额外的增殖研究表明，c-myc原癌基因的上调与胸苷摄取增加有关。这些数据表明，TNF-α诱导的骨髓前体细胞依赖IL-2的NK细胞生成增加与增殖增强以及IL-2受体和c-myc原癌基因的mRNA表达上调有关。
