摘要
目的研究辅助性T细胞（Th）22细胞在恶性腹水（MA）及同源外周血中的分布及其表型特征，探讨Th22细胞分化和募集浸润至腹腔的机制。方法流式细胞术检测Th22细胞在MA和外周血中的分布和表型。重组人细胞因子刺激MA和外周血中初始CD04^＋T细胞，观察其分化成Th22细胞的情况。检测外周血来源的CD04^＋T细胞在体外向MA上清液趋化，并加入人抗CC类趋化因子（CCL）20、抗CCL22、抗CCL27单克隆抗体观察阻断效应。结果MA中Th22细胞比例[（3.22±0.40）%，n＝37]明显高于对应外周血[（0.79±0.20）%，n＝37，P＝0.006）和健康对照组[（0.63±0.11）%，n＝10，P＝0.002]，Th17细胞在MA中比例[（3.30±0.18）%]也明显高于对应外周血[（0.79±0.15）%，n＝37，P＝0.008]及健康对照组[（0.67±0.12）%，n＝10，P＝0.001]，且两种细胞比例呈正相关（P＝0.002）。MA和外周血中Th22细胞的CD45RO、CC类趋化因子受体（CCR）4、CCR6和CCR10表达水平高于CD45RA、CD62L、CCR3、CCR5。CD4^＋T细胞向Th22细胞分化过程中，白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、IL-1β起促进作用，干扰素-γ（IFN-γ）起抑制作用，且Th22细胞受IL-6的促分化作用呈现时间剂量依赖性。MA上清液对外周血Th22细胞有明显的趋化效应，加入抗CCL20、抗CCL22、抗CCL27单克隆抗体则表现为阻断此趋化作用。结论MA中的趋化因子与炎性细胞因子在腹膜腔内共同作用使MA中Th22细胞比例明显高于外周血，Th22细胞可能参与MA的发病过程并发挥一定的免疫调节作用。
Objective To investigate the distribution and phenotypic characteristics of helper T-cell 22 （Th22） cells in malignant ascites （MA） and peripheral blood from hepatic carcinoma patients, and the mechanism by which Th22 cells differentiate and recruit into the peritoneal space.Methods To determine the distribution and phenotypic features of Th22 cells in MA and peripheral blood. Purified na？ve CD04^＋ T cells isolated from MA and peripheral blood were stimulated with cytokines. MA was used to stimulate chemotaxis of Th22 cells in the absence or presence of anti-chemokine ligand 20 （CCL20）, anti-CCL22, or/and anti-CCL27 mAbs.Results Th22 cells in MA [（3.22±0.40）%, n=37） were obviously higher than peripheral blood [（0.79±0.20）%, n=37, P=0.006） from MA patients and healthy controls [（0.63±0.11）%, n=10, P=0.002], Th17 cells in MA [（3.30±0.18）%] were obviously higher than peripheral blood [（0.79±0.15）%, n=37, P=0.008] from MA patients and healthy controls [（0.67±0.12）%, n=10, P=0.001] Th22 cells correlated positively with Th17 cells in MA （P=0.001）. Th22 cells expressed high levels of CD45RO, CC chemokine receptor （CCR） 4, CCR6 and CCR10, medium level of CCR7, and low levels of CD45RA, CD62L, CCR3 and CCR5 in MA. Th22 cells were facilitated by interleukin-6 （IL-6）, IL-1b, and/or tumor necrosis factor-α （IFN-α）, and inhibited by interferon-γ （IFN-γ） differentiate from CD04^＋ T cells. MA were chemotactic for Th22 cells, that could be interdicted by anti-CCL20, anti-CCL22, and anti-CCL27 mAbs.Conclusion Chemokines and cytokines may contribute to the increased Th22 cells in MA. Th22 cells probably participate in pathogenic mechanism of MA and may play an important role in immune regulation of human peritoneal malignant environment.
作者
卢威顺
覃山羽
姜海行
谭式辉
杨显文
罗薇
卢东红
Lu Weishun, Qin Shanyu, Jiang Haixing, Tan Shihui, Yang Xianwen, Luo Wei, Lu Donghong(Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China)
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2018年第3期424-427,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金（81260083、31360221）
关键词
辅助性T细胞22细胞
肝细胞癌
恶性腹水
趋化
分化
Helper T-cell 22 cells
Hepatic carcinoma
Malignant ascites
Chemotaxis
Differentiation
