中晚期鼻咽癌患者CD4＋，CD25＋T调节细胞及相关调节因子水平的免疫病理意义

Implications of the CD4 ~ and CD25 ~ positive regulatory T cells and its associated regulatory factors in immunopathology of patients with middle to late stage of nasopharyngeal carcinoma

目的探讨中晚期鼻咽癌患者外周血CD4＋CD25＋T调节细胞比例及转录因子叉头状螺旋转录因子（forkheadtranscriptionfactor3，Foxp3）和血清细胞因子转化生长因子p1（TGF—p1）和IL-10水平的免疫病理意义。方法分别应用流式细胞术（FCM）、逆转录-聚合酶链反应（RT—PCR）、ELISA方法检测中晚期鼻咽癌患者外周血单个核细胞中CD4＋CD25＋T调节细胞比例、Foxp3转录活性和血清TGF-[31、IL-10表达水平，并与健康人相应指标进行比较，分析其免疫病理意义。结果中晚期鼻咽癌患者外周血CD4＋CD25＋T调节细胞比例[（4．23±0．53）％V8（2．65±0．31）％，t=8．60，P〈0．01]、Foxp3转录活性（3．699±0．309VS1．109±0．146，t’=31．08，P〈0．05）、TGF—β1[（645．56±39．61）pg／mlvs（488．82±36．91）pg／ml，t=10．27，P〈0．01]及IL—10[（1．27±0．21）pg／mlVS（0．68±0．08）pg／ml,t’=10．61，P〈0．05]表达水平均明显高于健康人。结论CD4＋CD25＋T调节细胞、转录因子Foxp3和细胞因子TGF-β1、IL-10共同构成一个正反馈体系，促进了中晚期鼻咽癌患者肿瘤微环境中免疫耐受现象的发展及免疫逃逸的发生过程。

Objective To investigate the implications of ratio of the CD4 ＋ and CD25 ＋ positive regulatory T cells （ CD4 ＋ CD25 ＋ Tregs） in peripheral blood mononuclear cells （PBMC） and its associated regulatory factors such as forkhead transcription factor 3 （Foxp3） mRNA transcriptional activity in PBMC, serum levels of transforming growth factor beta-1 （ TGF-β1 ）, and interleukin 10 （IL-10） in the immunopathology of patients with middle to late staged nasopharyngeal carcinoma （NPC） based on a clinical trial. Methods In this study, 18 NPC cases at middle to late stage as observing group and 10 healthy persons as con- trol group were included to detect their ratio of the CD4 ＋ CD25 ＋ Tregs in the PBMC with flow cytometry （FCM） technique, transcriptional activity of Foxp3 with RT-PCR procedure, and serum levels of TGF-151 and IL-10 with enzyme-linked immunosorbent assay （ELISA） method. A comparative analysis was used to explore their implications in the immunopathological correlation of NPC cases with their lesion. Results The ratio of the CID4＋ CD25 ＋ Tregs to total CID4＋ T cells in PBMC was significantly increased [ （4. 23 ± 0. 53） % vs （2. 65 ± 0. 31 ） %, t = 8.60, P 〈 0. 01 ], accompanied with significantly elevated levels of Foxp3 transcription in PBMC （3. 699 ±0. 309 vs 1. 109 ±0. 146, t＇ =31.08, P 〈0. 05], and serum contents of TGF-β1 [ （645. 56 ± 39. 61 ） pg/ml vs （488. 82 ± 36. 91 ） pg/ml, t = 10. 27, P 〈 0. 01 ] and IL-10 [ （ 1.27±0. 21 ） pg/ml vs （0. 68 ± 0. 08） pg/ml, t＇ = 10. 61, P 〈 0. 05 ] in these patients, when compared with that of healthy controls. Conclusions It may be true that CID＋ CD25 ＋ Tregs, transcriptional regulatory factor Foxp3, and cytokines TGF-β1as well as IL-IO altogether were composed of a regulating system in a positive feedback way to promote the developing process of immunotolerance phenomena in the tumor mi- croenviromnent and the initiation of immunoescape among patients with middle to late staged nasopharyngeal carcinoma.