Lazenby A W, Roth J A, Owen-Schaub L B, Grimm E A
Department of Thoracic Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Cytokine. 1992 Nov;4(6):479-87. doi: 10.1016/1043-4666(92)90008-f.
Interleukin 1 is a pleuripotent cytokine shown to synergize with IL-2 in the generation of lymphokine-activated killer (LAK) cells, when cultured with human peripheral blood mononuclear cells (PBMC) or peripheral blood lymphocytes (PBL). When IL-1 and low dose IL-2 are added in combination, both LAK cytotoxicity and proliferation are increased in short-term (5-6 day) and long-term (12-14 day) cultures compared with cells activated with IL-2 alone. The purpose of this study was to examine the contribution of tumor necrosis factor (TNF-alpha), lymphotoxin (LT, or TNF-beta) and the TNF receptor in the observed IL-1/IL-2 mediated synergy. Analysis of lymphocyte culture supernatants using the L929 bioassay and by specific ELISAs demonstrated an increased production of both TNF and LT in those cells cultured with IL-1 and IL-2. Utilizing specific neutralizing antisera, our experiments demonstrated the biologic activity of both cytokines, with LT-specific antibodies producing the greatest diminution of IL-1/IL-2 stimulated cell proliferation and cytotoxicity. The addition of IL-1 and IL-2 in combination markedly upregulated TNF-receptor expression (measured by Scatchard analysis) in comparison with cells stimulated with IL-2 alone. Characterization of the TNF-R by flow cytometric analysis revealed increased membrane expression of the 75 kDa, but not the 55 kDa, TNF binding protein as a result of IL-1 costimulation.
白细胞介素1是一种多效性细胞因子，已证明当与人外周血单个核细胞（PBMC）或外周血淋巴细胞（PBL）一起培养时，它能在淋巴因子激活的杀伤（LAK）细胞的生成过程中与IL-2协同作用。当联合添加IL-1和低剂量IL-2时，与单独用IL-2激活的细胞相比，在短期（5 - 6天）和长期（12 - 14天）培养中，LAK细胞的细胞毒性和增殖都增加了。本研究的目的是检验肿瘤坏死因子（TNF-α）、淋巴毒素（LT，或TNF-β）以及TNF受体在观察到的IL-1/IL-2介导的协同作用中的贡献。使用L929生物测定法和特异性酶联免疫吸附测定（ELISA）对淋巴细胞培养上清液进行分析，结果表明在用IL-1和IL-2培养的细胞中，TNF和LT的产生均增加。利用特异性中和抗血清，我们的实验证明了这两种细胞因子的生物学活性，其中LT特异性抗体对IL-1/IL-2刺激的细胞增殖和细胞毒性的降低作用最为显著。与单独用IL-2刺激的细胞相比，联合添加IL-1和IL-2能显著上调TNF受体的表达（通过Scatchard分析测定）。通过流式细胞术分析对TNF-R进行表征，结果显示由于IL-1的共刺激作用，75 kDa的TNF结合蛋白的膜表达增加，而55 kDa的TNF结合蛋白的膜表达未增加。
