慢性HBV感染者外周血CXCR5~+CD4~+Tfh细胞的测定及其与FoxP3~+Treg细胞的相关性

目的:探讨慢性乙型肝炎病毒(hepatitis Bvirus,HBV)感染不同阶段患者外周血CD4+T淋巴细胞中CD4+CXCR5+Tfh细胞及CD4+CD25+FoxP3+Treg细胞的百分比及其意义.方法:应用流式细胞术检测15例慢性无症状HBV携带者(chronic asymptomatic HBV carriers,AsC)、42例慢性乙型肝炎(chronic hepatitisB,CHB)患者(HBeAg阳性25例、HBeAg阴性17例)、11例非活动性HBsAg携带者(inactive HBsAg carriers,InC)外周血CD4+CXCR5+Tfh细胞及CD4+CD25+FoxP3+Treg细胞占CD4+T淋巴细胞的百分比,并与15例健康对照(healthycontrol,HC)进行比较.结果:AsC、HBeAg(+)CHB、HBeAg(-)CHB组外周血CD4+CXCR5+Tfh细胞占CD4+T淋巴细胞的比例分别为17.66(15.34%-20.56%),21.95(19.60%-26.32%),22.33(17.58%-24.85%),显著高于HC组的13.67(9.80%-15.32%),差异具有统计学意义(P<0.001).与AsC及InC组的16.11(12.33%-19.73%)相比,HBeAg(+)、HBeAg(-)CHB组外周血CD4+CXCR5+Tfh细胞占CD4+T淋巴细胞的比例显著升高(P<0.05).此外,AsC组外周血CD4+CD25+FoxP3+Treg细胞占CD4+T淋巴细胞的比例为7.70(6.35%-9.13%),显著高于HC组的6.53(5.54%-7.35%),P<0.05.HBeAg(+)CHB组外周血CD4+T淋巴细胞中CD4+CD25+FoxP3+Treg细胞的频率为7.52(6.09%-8.49%),与AsC组相比呈降低的趋势.外周血CD4+CXCR5+Tfh细胞占CD4+T淋巴细胞的比例与HBVDNA载量呈负性相关(r=-0.275,P<0.05);而与血清ALT水平、HBsAg滴度无相关性.结论:CD4+CXCR5+Tfh细胞可能参与了慢性HBV感染所介导的免疫反应,外周血CD4+CD25+FoxP3+Treg细胞及CD4+CXCR5+Tfh细胞的消长可能与疾病的活动性相关.

Correlation between percentages of peripheral blood CD4~+CXCR5~+Tfh cells and those of FoxP3~+Treg cells in patients with chronic hepatitis B virus infection

AIM: To investigate the correlation between the percentages of blood CD4+CXCR5+Tfh cells and those of CD4+CD25+FoxP3+Treg cells in patients with chronic hepatitis B virus (HBV) infection.METHODS: Fresh peripheral blood samples were collected from 15 chronic asymptom- atic HBV carriers (AsC), 42 chronic hepatitis B (CHB) patients, of whom 25 were seropositive and 17 seronegative for HBeAg, 11 inactive HBsAg carriers (InC), and 15 healthy controls. The percentages of CD4+CXCR5+Tfh cells and CD4+CD25+FoxP3+Treg cells were measured by flow cytometry. RESULTS: The percentages of CD4+CXCR5+Tfh cells in total CD4+T cells isolated from AsC, HBeAg(+)CHB and HBeAg(-)CHB patients were significantly higher than that from healthy controls 17.66 (15.34%-20.56%), 21.95 (19.60%-26.32%), 22.33 (17.58%-24.85%) vs 13.67 (9.80%-15.32%), all P < 0.001]. The percentages of CD4+CXCR5+Tfh cells in HBeAg(+)CHB or HBeAg(-)CHB patients were elevated significantly compared to those in AsC or InC patients, 16.11 (12.33%-19.73%), P < 0.05. The percentage of CD4+CD25+FoxP3+Treg cells in AsC patients was significantly higher than that in healthy controls, 7.70 (6.35%-9.13%) vs 6.53 (5.54%-7.35%), P < 0.05. Meanwhile, there was a decreasing tendency of the percentages of CD4+CD25+FoxP3+Treg cells in HBeAg(+)CHB patients, 7.52 (6.09%-8.49%) compared to AsC patients. A negative correlation was found between the percentages of circulating CD4+CXCR5+Tfh cells and the HBV DNA load ( r = -0.275, P < 0.05), while no significant correlation was found between the percentages of circulating CD4+CXCR5+Tfh cells and ALT or HBsAg levels. CONCLUSION: CD4+CXCR5+Tfh cells may participate in chronic HBV-related immune response, and the relative bias between CD4+CD25+FoxP3+Treg cells and CD4+CXCR5+Tfh cells may correlate with disease activity.