肿瘤患者T细胞核仁嗜银蛋白和辅助性T细胞亚群变化

Changes of AgNORs expression of T lymphocytes and helper T cell subsets in peripheral blood mononuclear cells from cancer patients

目的 :探讨肿瘤患者外周血单个核细胞 (PBMC)中T细胞核仁嗜银蛋白 (AgNORs)表达和辅助性T(Th)细胞亚群变化的关系及其临床意义。方法 :采取肿瘤患者 86例、正常对照者 44例的外周血。PBMC经多克隆T细胞活化剂刺激 ,用图像分析法检测AgNORs区面积与细胞核仁面积的百分比 (I .S % ) ;PBMC用离子霉素和佛波醇酯活化 5h后 ,以酶联免疫斑点法 (ELISPOT)检测IFNγ和IL 4产生细胞的频度 (% ) ;用相同的活化剂刺激 2 4h ,用ELISA试剂盒检测培养上清液中的γ 干扰素 (IFNγ)和白细胞介素 4(IL 4)水平。结果 :肿瘤患者和正常人 ,AgNORs表达分别为 4.9± 1.2I .S %和 7.82± 1.2 8I .S % ,肿瘤组显著下降 (P <0 .0 5 ) ;肿瘤组PBMC中Th2细胞频度显著上升 ,Th1/Th2比值显著下降 ;同时 ,肿瘤组PBMC产生IFNγ和IL 4水平发生相应变化 ,变化方式与Th亚群变化相似 ;系统分析 5 1例肺癌 ,转移组比未转移组 ,复发组比未复发组 ,Th1细胞数、Th1/Th2和IFNγ产生水平显著下降 ;在肿瘤组AgNORs表达与Th1细胞频度、Th1/Th2、IFNγ产生和肿瘤患者生活状态的Karnofsky评分正相关。结论 :肿瘤患者PBMC中T细胞表达AgNORs下降 ,与患者Th1细胞功能下降呈正相关 。

Objective:To investigate the changes of silver stainng protein of nuclear organizer regions(AgNORs)expression of T lymphocytes and helper T (Th) cell subsets in peripheral mononuclear cells (PBMC) from cancer patients and to analyze their relationship as well as the significance.Methods:AgNORs expression in T cells activated with a multiple colonal activator was examined using a special image system.After activation of PBMC with ionomycin plus PMA for 5h, interferon γ (IFNγ) producing and interleukin 4 (IL 4) producing cell frequencies were detected with enzyme linked immunospot assay (ELISPOT); IFNγ and IL 4 production stimulated with ionomycin plus PMA for 24h were assayed with ELISA kits.Results:AgNORs expression of activated T cells in PBMC from cancer patients ( n =86) and healthy persons ( n =44) was 4.9±1.2 I.S% and 7.8±1.3 I.S%,respectively; Th2 frequency was significantly higher and the ratio of Th1 to Th2 frequency was more lower in cancer patient group. Moreover, the IFNγ production and IL 4 production in cancer patient group were changed in similar manner with Th subset frequencies; In lung cancer patients the AgNORs expression, Th1 frequency, Th1/Th2 ratio and IFNγ production were more significantly decreased in metastasis or in recurrence status.AgNORs expression in cancer patients correlated with their Th1 frequencies, Th1/Th2 ratio, IFNγ production levels and Karnofsky's estimators. Conclusion:In analyzed cancer patient cases, the expression of AgNORs and Th1 type cell function were significantly decreased and both closely correlated.