CD4＋CD25＋调节性T细胞在胃癌患者外周血分布的临床意义和作用机制

Distribution of CD4 ＋CD25 ＋ T Regulatory Cells in Peripheral Blood of Patients with Gastric Cancer

目的：探讨CD4＋CD25＋调节性T细胞在胃癌患者外周血分布的临床意义及其作用机制。方法流式细胞术分析不同TNM分期的胃癌患者和健康者外周血CD4＋CD25＋调节性T细胞的比例。免疫磁珠分离胃癌患者和健康者外周血CD4＋CD25＋调节性T细胞，将CD4＋CD25＋调节性T细胞与淋巴细胞体外共培养， CCK8方法检测CD4＋CD25＋调节性T细胞对淋巴细胞的增殖能力的影响。 RT-PCR检测CD4＋CD25＋调节性T细胞特异性转录因子Foxp3 mRNA的表达水平。结果胃癌患者外周血CD4＋CD25＋调节性T细胞的比例明显高于健康者，差异具有统计学意义（P＜0．05）。其中Ⅲ期和Ⅳ期胃癌患者外周血调节性T细胞的比例均明显高于Ⅰ-Ⅱ期胃癌患者，差异具有统计学意义（ P ＜0．05）。与健康者相比，胃癌患者 CD4＋CD25＋调节性T细胞能明显抑制淋巴细胞增殖，其差异具有统计学意义（ P＜0．05），而且Ⅲ期和Ⅳ期胃癌患者CD4＋CD25＋调节性T细胞抑制淋巴细胞增殖的能力明显强于Ⅰ-Ⅱ期胃癌患者，其差异具有统计学意义（P＜0．05）。进一步分析显示胃癌患者CD4＋CD25＋调节性T细胞Foxp3 mRNA的表达水平均明显高于健康者，差异具有统计学意义（P＜0．05）。其中Ⅲ期和Ⅳ期胃癌患者Foxp3 mRNA的表达水平明显高于Ⅰ-Ⅱ期胃癌患者，其差异具有统计学意义（P＜0．05）。结论调节性T细胞可能通过增强Foxp3 mRNA表达发挥免疫抑制作用，促进胃癌的发生发展。通过监测外周血调节性T细胞有利于评估胃癌患者免疫功能和病情进展。

Objective To explore the clinical significance and mechanism of CD4 ＋CD25 ＋ T regulatory cells in patients with gastric cancer. Methods The proportion of peripheral CD4 ＋CD25 ＋T regulatory cells was detected in 60 patients with gastric cancer at different TNM stages and 30 healthy subjects by flow cytometry. CD4 ＋CD25 ＋ T regulatory cells were isolated from patients with gastric cancer and healthy subjects by MACS, and cultured with lymphocytes in vitro. The effect of CD4 ＋CD25 ＋ T regulatory cells on the proliferation of lymphocytes was examined by CCK8 method and the expression levels of Foxp3 mRNA were measured by RT-PCR. Results The proportion of CD4 ＋CD25 ＋ T regulatory cells was significantly higher in patients with gastric cancer than in health-y subjects （ P〈0. 05 ） . Furthermore, it was significantly increased in patients at stage Ⅲ and stage Ⅳ when compared with those at stageⅠ-Ⅱ （ P〈0. 05 ） . CD4 ＋CD25 ＋ T regulatory cells in＆amp;nbsp;patients with gastric cancer could significantly inhibit the proliferation of lymphocytes when compari-son with those in healthy subjects （ P〈0. 05 ） . What ’ s more, the inhibitory effect of CD4 ＋CD25 ＋ T regulatory cells on the lymphocyte growth was significantly stronger in patients at stage Ⅲand stage Ⅳ than in patients at stageⅠ-Ⅱ （ P〈0. 05 ） . The mRNA levels of Foxp3 were signifi-cantly higher in CD4 ＋CD25 ＋ T regulatory cells in patients with gastric cancer than those in healthy subjects （ P〈0. 05 ） . It was significantly increased in patients at stageⅢand stageⅣwhen com-pared with those at stageⅠ-Ⅱ （ P〈0. 05 ） . Conclusion T regulatory cells may inhibit the im-mune response by up-regulating the Foxp3 expression and promote the development of gastric canc-er. Monitoring T regulatory cells will help to evaluate the immune function of patients with gastric cancer and the development of the disease.