Dynamic Changes Of T-cell Immunity In Women With Chronic HBV Infection During Pregnancy And Postpartum And Its Relationship With HBV Infection Status

Background and Aims:The natural history and disease progression of hepatitis B virus(HBV)infection depend on the interaction between the immune system and the virus.Pregnancy,a spe cial physiological process,can change the maternal immune status.For pregnant wom en with chronic HBV infection,it is still unclear how the maternal immune system ch anges during pregnancy and postpartum,and whether this change will lead to changes in HBV infection status and disease progression.Firstly,this study will analyze the d ynamic changes of T-cell immunity in women with chronic HBV infection from preg nancy to postpartum and their correlation with virological and liver biochemical para meters.Secondly,this study attempted to explore the immunological characteristics o f CD4+T cells in ALT-Flare mothers.Method:In this prospective study,we enrolled 24 HBeAg+ pregnant women who were in the stage of immune tolerance(IT)at 21-32 weeks of gestation and followed up from pregnancy to 4-6 months postpartum.As control,we enrolled 12 HBeAg+non-pregna nt women in the stage of IT at the same time.We tested the dynamic changes of the p henotype and function of T cell subsets by flow cytometry during follow-up,and anal yzed the correlation between parameters of T cell immunity and clinical laboratory.B esides,we compared the differences of immunological characteristics of CD4+T cells between ALT-Flare mothers and Non-ALT-Flare mothers.Results:1.By analyzing the dynamic change of CD4+T lymphocyte cells phenotype and function,we found that the frequency of Th1(CD4+CXCR3+)subset was significantly lower during pregnancy than that after delivery(p=0.000).Conversely,the frequenc y of Th2 subset(CD4+CCR6-CXCR3-)was significantly higher during pregnancy tha n that after delivery(p=0.000).However,Th17(CD4+CCR6+)frequency has no stati stical difference(p=0.341).In the analysis of differentiation stages of Th1 memory c ells,we found that the central memory T cells(TCM)were dominant during pregnanc y and effector memory T cells(TEM)were dominant after delivery.2.The ability of CD4+T cells to secrete IL-17 in the later stages of pregnancy w as significantly higher than that in the postpartum(p=0.008,p=0.009).Interestingly,we found a group of special Th2 subset that can secrete IL-17.3.Th1 frequency and the level of IL-17 were negatively correlated with the level of HBeAg(p=0.045,r=-0.442.P=0.004,r=-0.638).4.In the non-ALT-Flare group,Th1 frequency decreased during pregnancy and i ncreased postpartum.In contrast,Th2 frequency increased during pregnancy and decr eased postpartum.The frequency of the TCM cells in Th1 subset increased during pre gnancy and decreased postpartum,and TEM cells decreased during pregnancy and in creased postpartum.The ability of CD4+T cells to secrete IL-17 at 32-40 weeks of ges tation was significantly higher than that of postpartum(p=0.000).However,these dyn amic changes were not observed in the ALT-Flare group.5.At 32-40 weeks of gestation and 4-6 months after delivery,Th2 frequency of ALT-Flare group was significantly higher than that of Non-Flare group(p=0.007,p=0.038).But its ability to secrete IL-4 was lower.Besides,in the group of ALT-Flare,th e ability of Treg to secrete IL-10 was significantly lower than that of Non-Flare group at 4-6 months after delivery(p=0.016).6.In the Non-ALT-Flare group,the ability of Thl subset to secrete IFN-y was po sitively correlated with the ability of Treg to secrete IL-10(p=0.017,r=0.668).Conver sely,in the ALT-Flare group,the ability of Thl subset to secrete TNF-α was negative ly correlated with the ability of Treg to secrete IL-10(p=0.020,r=-0.883).Conclusions:1.T cell immunity experiences dynamic change from pregnancy to postpartum,with domination of anti-inflammatory reaction during pregnancy and domination of t he pro-inflammatory reaction after delivery.The changes of T cell immunity might af fect the change of virological and liver biochemical parameters.2.The mothers in the ALT-Flare group had an imbalance in immune regulation,showing stronger pro-inflammatory and weaker anti-inflammatory responses,which may be involved in the pathophysiology of liver inflammation.