Luger T A, Uchida A, Köck A, Colot M, Micksche M
J Immunol. 1985 Apr;134(4):2477-83.
Normal as well as transformed epidermal cells (EC) have recently been reported to produce a cytokine--EC-derived thymocyte-activating factor (ETAF), which according to its biologic as well as biochemical properties is indistinguishable from macrophage-derived interleukin 1 (IL 1). In the present study, the effect of supernatants (SN) derived from normal EC and a human squamous carcinoma cell (SCC) line were tested for their effects on natural killer (NK) cell activity. EC- as well as SCC-derived SN were able to augment in vitro NK cell activity of peripheral blood lymphocytes against K 562 cells. In contrast, adherent cell-derived, IL 1-containing SN did not affect NK cell activity. Upon high-pressure liquid chromatography (HPLC) gel filtration, ETAF and the EC-derived NK cell activity-augmenting factor (ENKAF) exhibited a similar m.w. However, by using reverse-phase HPLC, ETAF and ENKAF eluted as distinct peaks of activity, indicating that SCC cell-derived ENKAF is different from ETAF. Furthermore, ENKAF does not contain interleukin 2 (IL 2) or interferon (IFN) activity. The enhancement of NK cell activity was dose dependent and evident after 20 hr of preincubation of effector cells. Pretreatment of target cells with ENKAF did not affect the susceptibility of the target cells. The NK activity of large granular lymphocytes (LGL) purified by discontinuous Percoll gradient centrifugation and further depleted of high-affinity sheep erythrocyte rosetting cells was enhanced by ENKAF. In contrast, no NK cell activity was expressed by LGL-depleted T cell populations before or after treatment with ENKAF. In a single cell cytotoxicity assay in agarose, the number of lymphocyte binding to K 562 was not affected by ENKAF, but the frequency of dead conjugated target cells and presumably of active killer cells was increased by pretreatment with ENKAF. Additional incubation of LGL with ETAF did not further increase ENKAF-mediated augmentation of NK activity. In contrast to ETAF, ENKAF was not chemotactic for polymorphonuclear leukocytes. These results indicate that normal as well as transformed EC release a unique cytokine--ENKAF--which augments NK cell activity of LGL but is distinct from ETAF, IL 2, and IFN.
最近有报道称，正常表皮细胞以及转化表皮细胞（EC）可产生一种细胞因子——EC衍生的胸腺细胞激活因子（ETAF），根据其生物学和生化特性，它与巨噬细胞衍生的白细胞介素1（IL 1）无法区分。在本研究中，测试了来自正常EC和人鳞状癌细胞（SCC）系的上清液（SN）对自然杀伤（NK）细胞活性的影响。EC以及SCC衍生的SN能够增强外周血淋巴细胞对K 562细胞的体外NK细胞活性。相比之下，贴壁细胞衍生的含IL 1的SN不影响NK细胞活性。经高压液相色谱（HPLC）凝胶过滤后，ETAF和EC衍生的NK细胞活性增强因子（ENKAF）表现出相似的分子量。然而，通过反相HPLC，ETAF和ENKAF以不同的活性峰洗脱，表明SCC细胞衍生的ENKAF与ETAF不同。此外，ENKAF不含有白细胞介素2（IL 2）或干扰素（IFN）活性。NK细胞活性的增强呈剂量依赖性，在效应细胞预孵育20小时后明显。用ENKAF预处理靶细胞不影响靶细胞敏感性。通过不连续Percoll梯度离心纯化并进一步去除高亲和力绵羊红细胞花环形成细胞的大颗粒淋巴细胞（LGL）的NK活性被ENKAF增强。相比之下，在ENKAF处理之前或之后，去除LGL的T细胞群体均未表现出NK细胞活性。在琼脂糖单细胞细胞毒性试验中，与K 562结合的淋巴细胞数量不受ENKAF影响，但经ENKAF预处理后，死结合靶细胞以及可能的活性杀伤细胞的频率增加。LGL与ETAF的额外孵育并未进一步增加ENKAF介导的NK活性增强。与ETAF不同，ENKAF对多形核白细胞没有趋化作用。这些结果表明，正常以及转化的EC释放一种独特的细胞因子——ENKAF，它可增强LGL的NK细胞活性，但与ETAF、IL 2和IFN不同。
