摘要
目的探讨CD4^+CD25^+调节性T淋巴细胞(CD4^+CD25^+Treg)在HCC患者外周血及肿瘤组织中的频率、抑制功能及临床意义。方法收集18例原发性HCC患者的PBMC、肝癌组织及相应的癌旁组织标本,以及10例CHB患者和15名健康对照的外周血标本,以三色与四色流式分析法分析PBMC以及肿瘤浸润的淋巴细胞中CD4^+CD25^+Treg的频率及表型,并同时分析其与HBV持续感染、肿瘤TNM分期和其他临床指标的关系,用BrdU掺入法评价CD4^+CD25^+Treg的免疫抑制功能。结果与健康对照组相比HCC患者、慢性HBV感染者外周血中CD4^+CD25^+Treg频率明显上升(P<0.01),且HCC患者肿瘤浸润的淋巴细胞中CD4^+CD25^+Treg的频率也明显上调(P<0.01);随着肿瘤的进展HCC患者外周血中CD4^+CD25^+Treg呈上升趋势(P<0.05); HCC患者CD4^+CD25^+Treg可非特异性地抑制自身活化的CD4^+CD25^- T淋巴细胞,并呈剂量依赖性,且抑制能力与健康对照组相比差异无统计学意义。结论HCC患者外周血中及肿瘤组织中CD4^+CD25^+Treg的频率升高,增多的CD4^+CD25^+Treg可能参与抑制抗HCC的免疫应答,从而使肝癌细胞逃脱机体的“免疫监视”作用。
Objectives (1) To evaluate the prevalence, phenotypes and suppressive function of CD4^+CD25^+ regulatory T cells (Tregs) among the in peripheral blood mononuclear cells (PBMCs) and tumor- infiltration lymphocytes (TILs) from hepatocellular carcinoma (HCC) patients and patients with chronic hepatitis B. (2) To investigate the correlation between the frequency of CD4^+CD25^+ Tregs and clinical characteristics of HCC patients. Methods PBMCs and TILs in 18 HCC patients, 10 chronic hepatitis B (CHB) patients and 15 healthy donors were evaluated for the phenotypes of CD4^+CD25^+ Tregs and the proportion of CD4^+CD25^+ Tregs as a percentage of the total CD4^+ cells, by flow cytometric analysis with three or four color staining. The relationship between the frequency of CD4^+CD25^+ Tregs and tumor TNM stages was analyzed. The CD4^+CD25^+ Tregs and CD4^+CD25^+ T cells were isolated from PBMC of HCC patients and donors. The suppressive function of CD4^+CD25^+ Tregs was analyzed. Results The percentages of CD4^+CD25^+ Tregs of the HCC patients (6.38% ± 6.30%) and CHB patients (4.29% ± 1.82%) were significantly higher than those of the healthy donors (1.58% ± 0.55%, P 〈 0.01). Among the TILs, the percentage of CD4^+CD25^+ Tregs was higher (t = 4.39, P 〈 0.01). There were significant differences in the prevalence of CD4^+CD25^+ Tregs in early and advanced stage HCCs (stage Ⅱ vs. Ⅲ, P 〈0.05; stage Ⅱ vs. Ⅳ P 〈0.01). The proliferative capacity of CD4^+CD25^+ T cells was inhibited by the presence of CD4^+CD25^+ T cells in a dose-dependent manner where the level of suppression was correlated to the ratio of the two-cell populations. Conclusion These results suggest that the increase in frequency of CD4^+CD25^+ Tregs might play a role in the suppression of the immune response against HCC, which may contribute to the HCC cells that escaped from immunological surveillance.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2007年第4期266-272,共7页
Chinese Journal of Hepatology
基金
973资助项目(2005CB522902)
北京市科技计划项目(H030230150130)
国家自然科学基金(30640091)
志谢 北京大学血液病研究所常燕老师在流式细胞仪检测中提供的帮助
关键词
癌
肝细胞
T淋巴细胞
肝炎
乙型
慢性
Carcinoma, hepatocellular
T lymphocytes
Chronic hepatitis B