Th17/CD4+CD25+调节性T淋巴细胞失衡在EB病毒相关噬血细胞综合征中的作用及临床意义

摘要

目的 探讨Th17细胞、CD4+CD25+调节性T淋巴细胞(Treg)及其相关转录因子、细胞因子水平变化在EB病毒(EBV)相关噬血细胞综合征(HLH)中的作用及临床意义.方法 研究对象为2012年1月—2016年12月在我院血液肿瘤科新诊断的EBV相关HLH患儿32例,及同期来我院体检的健康儿童30例.采用流式细胞术测定外周血T淋巴细胞中Th17细胞和Treg细胞的表达;用实时荧光定量PCR技术测定外周血单个核细胞中RORγt及Foxp3 mRNA的表达水平;采用ELISA法检测血清IL-6、IL-17、IL-10、TGF-β1水平.结果 EBV相关HLH组患儿的Th17细胞[(1.09±0.43)％vs(0.39±0.19)％]和RORγt mRNA水平[(1.41±0.37)vs(0.67±0.13)]明显高于对照组(P<0.05),Treg细胞[(3.66±1.13)％vs(6.80±1.15)％]和Foxp3 mRNA水平[(15.97±5.11)vs(30.23±4.95)]明显低于对照组(P<0.05).在治疗后,Th17细胞和RORγt mRNA水平较治疗前明显降低,Treg细胞和Foxp3 mRNA水平则较治疗前明显升高(P<0.05).EBV相关HLH组患儿血清IL-6、IL-17水平与对照组比较明显升高,而IL-10、TGF-β1水平则较对照组明显降低(P<0.05).结论Th17/Treg细胞失衡可能在EBV相关HLH的发病过程中起到了重要作用,维持Th17/Treg平衡的相关细胞因子可作为疾病变化的观察指标.%Objective To investigate the changes in Th17 cells and CD4+CD25+regulatory T lym-phocytes ( Treg) as well as transcription factors and cytokines relating to them in children with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) and to analyze their role and clinical significance. Methods Thirty-two children with newly diagnosed EBV-associated HLH in the Hematology/Oncology Department of Zhengzhou Children′s Hospital from January 2012 to December 2016 were enrolled in this study. Thirty healthy children taking physical examination in the same hospital in the corresponding period were recruited as controls. Percentages of Th17 and Treg cells in peripheral blood T lymphocytes were detected by flow cytometry. Expression of RORγt and Foxp3 at mRNA level in peripheral blood mononuclear cells was detected by real-time PCR. Levels of IL-6, IL-17, IL-10 and TGF-β1 in serum samples were measured by ELISA. Results Compared with the control group, the EBV-associated HLH group showed in-creased percentage of Th17 cells [(1. 09±0. 43)％ vs (0. 39±0. 19)％, P<0. 05] and enhanced expres-sion of RORγt at mRNA level [(1. 41±0. 37) vs (0. 67±0. 13), P<0. 05], but decreased percentage of Treg cells [(3. 66±1. 13)％ vs (6. 80±1. 15)％, P<0. 05] and inhibited expression of Foxp3 at mRNA level [(15. 97±5. 11) vs (30. 23±4. 95), P<0. 05]. All of the above mentioned changes were reversed af-ter treatment (P<0. 05). Serum levels of IL-6 and IL-17 of EBV-associated HLH group were higher than those of control group, while serum levels of IL-10 and TGF-β1 were lower (P<0. 05). Conclusion Im-balanced Th17/Treg cells might play an important role in the pathogenesis of EBV-associated HLH. Cyto-kines relating to the maintenance of Th17/Treg cell balance could be used as indicators of disease develop-ment.