CIN宫颈组织中Treg细胞和Th1/Th2细胞因子的表达及意义

Expression and Significance of Treg Cells and Th1 and Th2 Cytokines In the Cervix of CIN

目的探讨宫颈上皮内瘤变(CIN)宫颈组织中Treg细胞和Th1/Th2细胞因子的表达及其临床意义。方法对189例妇女行HPV检测、宫颈TCT检查及宫颈活检后行CIN病变分级,应用Q-PCR、流式细胞术,检测各组患者宫颈组织中IL-2、IL-4、IFN-γ、IL-10、IL-12的含量和Treg细胞表达。结果 81例良性病变、60例CINⅠ、27例CINⅡ和21例CINⅢ患者中高危型HPV感染例数分别为17(21%)、25(42%)、24(89%)和20(95%)例。良性病变、CINⅠ、CINⅡ和CINⅢ宫颈组织中,Treg细胞占CD4+T细胞的比例随病变程度增加而增加、IL-10表达水平逐渐上升、IFN-γ表达水平逐渐下降(P<0.05),IL-2、IL-12及IL-4的表达水平在4组患者中无明显差别。结论 CIN患者宫颈黏膜中Th1/Th2平衡向Th2方向漂移,Treg细胞表达增强,下调机体抗HPV感染和抗肿瘤免疫反应,促进CIN病变的进行性发展。

Objective To study the clinical significance of the level of regulatory T（Treg） cells and Th1 and Th2 cytokines in cervical mucosal of cervical intraepithelial neoplasia（CIN） patients.Methods Human papillomavirus（HPV） testing,thinprep cytologic test（TCT） and cervical biopsy were performed in cervical mucosal from 189 women and then all patients were classified as benign,CIN Ⅰ,Ⅱ,or Ⅲ.Flow cytometry was used to assess the percentages of Treg cells in CD4 ＋ T cells in the cervical mucosal and quantitative PCR was used to analysis the cervical mRNA expression of IL-2,IL-4,IFN-γ,IL-10 and IL-12.Results The numbers of women testing positive for high-risk HPV types were 17（21%） among women with benign（81）,and 25（42%） among women with CINⅠ（60）,and 24（89%） among women with CINⅡ（27） and 20（95%） among women with CIN Ⅲ（21）.Associated with increased odds of having high-grade cervical disease（benign,CINⅠ,CINⅡand CINⅢ）,the percentages of Treg cells in CD4 ＋ T cells in the cervical mucosal were gradually higher,the expressions of IL-10 were significantly higher and IFN-γ expressions were gradually lower（P 0.05）.No significant difference was found in the expression of IL-2,IL-12 and IL-4 among the groups with different pathological type and grade.Conclusion These results indicate that a shift to a Th2-type cytokine pattern during the development of CIN.Diminished cellular immunity and anti-HPV infection in the cervical mucosa and mucosal enrichment of Treg cells all contribute to the development of high-grade CIN lesions.