替比夫定对慢性乙型肝炎患者外周血CD4＋ CD25＋ CD127(low) T和CD8＋ CD25＋ T细胞频率的影响及临床意义  

The effect of telbivudine on peripheral blood CD4^+ CD25^+ CD127^(low) T cells and CD8^+ CD25^+ T cells and its clinical significance

作　　者：张梦军[1] 周吉军[1,2] 傅晓岚 王莉[1] 李杰[3] 牛微[1] 张小敏[1,2] 吴玉章 

机构地区：[1]第三军医大学全军免疫学研究所,重庆400038 [2]重庆西南医院感染科,重庆400038 [3]第三军医大学全军免疫学研究所学员旅7队,重庆400038

出　　处：《免疫学杂志》2010年第7期594-597,共4页Immunological Journal

基　　金：国家自然基金资助项目(30872352)

摘　　要：目的探讨核苷类药物替比夫定对慢性乙肝患者(CHB)外周血中CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例的影响,并结合临床指标分析其临床意义。方法替比夫定抗病毒治疗22例CHB患者,在治疗前及治疗后3,6个月时,分别以流式细胞仪检测外周血中CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例,实时荧光定量RT-PCR检测Foxp3 mRNA的表达水平,荧光定量PCR检测血清HBV DNA水平,酶联免疫吸附法检测HBV标志物,全自动生化分析仪检测ALT水平。结果 CHB患者外周血中CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例显著高于对照组。替比夫定治疗3个月时,这两群细胞比例显著下降,Foxp3 mRNA的表达也显著下降;HBV DNA水平降至检测水平以下的CHB患者,其CD4+CD25+CD127lowT细胞也降至正常水平。治疗3、6个月时,HBeAg阴转率分别为9.1%和18.2%,发生HBeAg血清学转换者的CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例均降至正常水平。结论替比夫定能快速有效抑制CHB患者的病毒复制,同时CD4+CD25+CD127lowT细胞和CD8+CD25+T细胞比例显著下调,可能降低了Treg对HBV特异性T淋巴细胞的抑制作用,改善了机体的免疫应答。This study aimed to investigate the effects of telbivudine on peripheral blood CD4＋ CD25＋ CD127 low T cells and CD8＋ CD25＋ T cells and its significance in patients with chronic hepatitis B.Twenty-two HBeAg positive chronic hepatitis B patients were recruited and received telbivudine treatment.Before and during the 3 or 6 months of treatment,the proportion of peripheral blood CD4＋ CD25＋ CD127 low T cells and CD8＋ CD25＋ T cells was detected by flow cytometry;the levels of HBV DNA in the serum were assayed by real-time PCR;the levels of Foxp3 mRNA were measured by real-time RT PCR;markers of hepatitis B virus infection were detected by ELISA assay and levels of alanine aminotransferase in the serum were measured.The proportion of peripheral blood CD4＋ CD25＋ CD127 low T cells and CD8＋ CD25＋ T cells in patients with CHB was significantly higher than that in healthy controls and decreased after 3 or 6 months of telbivudine treatment to a level comparable to that of the healthy controls.The levels of HBV DNA in patients,whose proportion of peripheral blood CD4＋ CD25＋ CD127 low T cells was also decreased to a level comparable to that of the healthy control,were undetectable.Three and six months of telbivudine treatments resulted in HBeAg negativity in 2 patients（9.1%） and 4 patients（18.2%）,respectively.All these results indicate that telbivudine treatment not only reduce serum HBV DNA levels rapidly and profoundly,but also indirectly affect immune system by downregulating the proportion of peripheral blood CD4＋ CD25＋ CD127 low T cells and CD8＋ CD25＋ T cells markedly,which is probably beneficial to restore antivirus immune response.

关 键 词：慢性乙型肝炎 替比夫定 CD4+CD25+CD127lowT细胞 CD8+CD25+T细胞 

分 类 号：R512.62[医药卫生—内科学]