Puri R K, Finbloom D S, Leland P, Mostowski H, Siegel J P
Division of Cytokine Biology, CBER/FDA, Bethesda, MD 20892.
Immunology. 1990 Aug;70(4):492-7.
Since interleukin-2 (IL-2) and IL-4 act in concert to support the development of cytotoxic T lymphocytes (CTL) and the generation of antigen-specific tumour infiltrating lymphocytes (TIL), we investigated the interaction of these cytokines with an established TIL line. TIL proliferated in an additive fashion in response to suboptimal concentrations of IL-2 and various concentrations of IL-4. TIL possessed high-affinity IL-4 receptors whether cultured in recombinant IL-2 (rIL-2) or rIL-4, but cells cultured in rIL-2 had higher numbers of IL-4 receptors than cells cultured in rIL-4. When TIL were cultured in increasing concentrations of rIL-2, a dose-dependent enhancement in IL-4 receptor number was observed. The maximum induction of IL-4 receptor expression was achieved by 4 hr of incubation with rIL-2 and was completely blocked by cycloheximide. Other cytokines, such as rIL-1, recombinant tumour necrosis factor (rTNF), recombinant interferon-alpha (rIFN-alpha) and rIFN-gamma, had no effect on IL-4 receptor number. rIL-2 also up-regulated IL-4 receptors on CTLL-2, a murine CTL line. These data indicate that high-affinity IL-4 receptors exist on murine TIL and they can be up-regulated by IL-2. Our observation that IL-2 up-regulates IL-4 receptor may help explain the additive effects of these lymphokines on the proliferation of TIL and other cell lines. It may also help explain their co-operative effects on the generation of antigen-specific TIL and the differentiation of CTL.
由于白细胞介素-2（IL-2）和IL-4协同作用以支持细胞毒性T淋巴细胞（CTL）的发育以及抗原特异性肿瘤浸润淋巴细胞（TIL）的产生，我们研究了这些细胞因子与已建立的TIL系的相互作用。TIL对次优浓度的IL-2和各种浓度的IL-4以累加方式增殖。无论在重组IL-2（rIL-2）还是rIL-4中培养，TIL都具有高亲和力的IL-4受体，但在rIL-2中培养的细胞比在rIL-4中培养的细胞具有更多的IL-4受体。当TIL在浓度不断增加的rIL-2中培养时，观察到IL-4受体数量呈剂量依赖性增加。用rIL-2孵育4小时可实现IL-4受体表达的最大诱导，并且该诱导被环己酰亚胺完全阻断。其他细胞因子，如rIL-1、重组肿瘤坏死因子（rTNF）、重组干扰素-α（rIFN-α）和rIFN-γ，对IL-4受体数量没有影响。rIL-2还上调了小鼠CTL系CTLL-2上的IL-4受体。这些数据表明小鼠TIL上存在高亲和力的IL-4受体，并且它们可以被IL-2上调。我们观察到IL-2上调IL-4受体这一现象可能有助于解释这些淋巴因子对TIL和其他细胞系增殖的累加效应。这也可能有助于解释它们对抗原特异性TIL产生和CTL分化的协同作用。
