Cross regulation by IL-10 and 1L-2/IL-12 of the helper T cells and the cytolytic activity of lymphocytes from malignant effusions of lung cancer patients
Cross regulation by IL-10 and 1L-2/IL-12 of the helper T cells and the cytolytic activity of lymphocytes from malignant effusions of lung cancer patients
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DOI：
10.1378/chest.112.4.960
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发表时间：
1997-10-01
期刊：
影响因子：
9.6
通讯作者：
Perng, RP
中科院分区：
文献类型：
--
作者：
Chen, YM;Yang, WK;Perng, RP
研究目的：我们之前的报告表明，肿瘤胸腔积液中存在局部细胞免疫损伤，白细胞介素-10 （IL-10）升高，IL-12检测不到。这些发现表明，局部免疫反应倾向于t辅助2型（Th2）途径而不是Th1途径。本研究旨在研究IL-2和/或IL-12治疗是否可以控制局部细胞免疫，并确定它们对辅助性t细胞途径和积液相关淋巴细胞（EALs）的细胞溶解活性的影响。设计：利用4例肺腺癌患者的恶性胸腔积液，采用Ficol-Hypaque离心，再进行Percoll密度离心，从EALs中分离肿瘤细胞。为了检测IL-2和/或IL-12培养是否能增强淋巴细胞的细胞溶解功能，我们将淋巴细胞与重组IL-2（含/不含IL-12）孵育6天。随后，在夜间（51）铬释放试验中评估杀肿瘤活性。测定特异性抗肿瘤活性的靶细胞为自体肿瘤细胞、对淋巴因子激活杀伤细胞敏感的Daudi细胞和对nk敏感的K562细胞。测量和结果：在体外用IL-2、IL-12或IL-2 + IL-12治疗后，Th通路从Th2型转变为Th1型（γ -干扰素产生增加）。为了进一步研究细胞因子处理对EALs细胞杀伤活性的影响，我们发现，在培养6天后，EALs无法杀死三种肿瘤靶点中的任何一种，而培养6天后的外周血淋巴细胞（pbl）对三种肿瘤靶点均具有低水平的细胞毒性。单独使用IL-2刺激可部分恢复EALs杀死肿瘤靶点的免疫能力。单独刺激IL-12对其细胞溶解活性无显著影响。然而，IL-12与IL-2协同作用可提高EALs和pbl对自体肿瘤靶点的细胞溶解活性。在Daudi细胞和K562细胞中没有发现这种协同作用。结论：这些结果表明，在低浓度IL-2存在下，IL-12激活EALs，将EALs从Th2途径转化为Th1途径，可能成为癌症过继免疫治疗的抗肿瘤效应物的替代来源。
Study objective: Our previous report demonstrated that there was impairment of local cellular immunity with elevated interleukin-10 (IL-10) and undetectable IL-12 in neoplastic pleural effusion. These findings suggest that the local immune reactions favor the T-helper type 2 (Th2) pathway instead of Th1 pathway. The present study was designed to examine whether local cellular immunity could be manipulated by IL-2 and/or IL-12 treatment, and to determine their effect on the helper T-cell pathways and the cytolytic activity of the effusion-associated lymphocytes (EALs).Design: Using malignant pleural effusions obtained from four patients suffering from adenocarcinoma of lung, we separated the tumor cells from the EALs with Ficol-Hypaque centrifugation, followed by Percoll density centrifugation. To test whether the cytolytic function of lymphocytes could be enhanced by culturing with IL-2 and/or IL-12, lymphocytes were incubated with recombinant IL-2 with/without IL-12 for 6 days. Following this, the tumoricidal activity was assessed in an overnight (51)chromium-release assay. Autologous tumor cells for measuring specific antitumor activity, Daudi cells susceptible to lymphokine-activated killer cells, and NK-susceptible K562 cells were used as target cells.Measurements and results: After treatment in vitro with IL-2, IL-12, or IL-2 plus IL-12, the Th pathway shifted from Th2 to Th1 type (increased gamma-interferon production). To further study the effect of cytokine treatment on the cytolytic activity of EALs, it was found that after 6-day culturing, the EALs failed to kill any of the three tumor targets, whereas the 6-day cultured peripheral blood lymphocytes (PBLs) gave low level of cytotoxicity against all three tumor targets. Stimulation with IL-2 alone partially restored the immunocompetence of EALs to kill the tumor targets. Stimulation with IL-12 alone showed no significant effect on their cytolytic activity. However, IL-12 synergized with IL-2 to increase the cytolytic activity of EALs and PBLs against autologous tumor targets. This synergistic effect was not found for Daudi cells and K562 cells.Conclusions: These result suggest that EALs activated with IL-12 in the presence of a low concentration of IL-2, which converted the EALs from Th2 pathway to Th1 pathway, could be an alternative source of antitumor effectors for adoptive immunotherapy of cancer.