A Study Of Acquired Cellular Immunity In Patients With Chronic Hepatitis B Achieved HBV-DNA <1000 IU/ml,HBeAg Loss,HBsAg<3000 IU/ml With Nucleot (S) Ide Treatment

ObjectiveTo investigate whether the acquired cellular immunity is restored in patients with chronic hepatitis B(CHB)who are treated with nucleot(s)ide analogue(NA)and achieve HBV-DNA<1000IU/ml,HBeAg disappearance and HBsAg <3000IU / ml and compare the acquired cellular immune in treated patients with that in the same virological indicators of immune control of patients with CHB,and to explore the relationship between acquired cellular immunity and HBsAg titer in patients with CHB treated with NA.We examined the frequency of different subtypes of circulating CD4+ and CD8+ T cells and their surface molecules in patients with chronic hepatitis B virus(HBV).Methods30 patients with CHB treated with NA: 0.05 IU/ml <HBsAg <3000 IU/ml,HBV-DNA <1000 IU/ml or below detection limit,HBeAg negative;20 patients with immune control of CHB: 0.05 IU/ml<HBsAg<3000 IU/ml,HBV-DNA<1000 IU/ml or below detection limit,HBeAg negative;l4 patients with flare of CHB: HBV-DNA>2000 IU/ml,HBsAg positive> 6 months,and serum transaminase(ALT and AST)is abnormal;13 healthy volunteers.The frequency of circulating TN、TCM、TEM、TE、TH1、TH2、TH17 and Treg cells and surface molecules of Tim3,PD-1 and CTLA4 on CD4+ and CD8+ T cells were measured by flow cytometry in different groups of patients and healthy control group.Results(1)The frequency of CD4+TCM cells was increased and the frequency of CD4+TE cells was decreased in NA treatment group compared with that in healthy control group.There was no significant difference in the frequencies of subtypes of CD8+T cells among the four groups.(2)There were no significant differences in the frequencies of TH1 and TH2 among the four groups.The frequency of TH17 cells in NA treatment group was lower than that in the flare of CHB group and higher than that in the healthy control group,and no difference was found between NA treatment group and immune control of CHB group.The frequency of CD4+CD25+ CD127 dimTreg cells in NA treatment group was higher than that in the flare of CHB group and lower than that in the healthy control group,and no difference was found between NA treatment group and immune control of CHB group.The expression of CCR4 on CD25 hiTreg cells in NA treatment group was higher than that in healthy control group,and there was no significant difference among NA treatment group,flare of CHB group and immune control of CHB group.(3)The ratio of TH1/TH2 was not significantly different among the four groups;The ratio of Treg/TH17 in NA treatment group and flare of CHB group was significantly lower than that in the healthy control group,and no significant difference was found between NA treatment group and immune control of CHB group.(4)No significant difference in PD-1 expression on CD4+ and CD8+T cells was found among the four groups.There was no significant difference in CTLA4 expression on CD4+ and CD8+T cells between NA treatment group and the flare of CHB group.The expression of CTLA4 on CD4+ and CD8+ T cells in NA treatment group was significantly higher than that in healthy control group,and slightly higher than that in the immune control of CHB group.The expression of Tim3 on CD4+T cells in NA treatment group was significantly higher than that in immune control of CHB group.(5)There was a positive correlation between serum HBsAg titer and frequency of CD4+CD25+Treg cells in NA treatment group.The serum HBsAg titer was positively correlated with the expression of Tim3 on CD4+ and CD8+T cells and negatively correlated with the expression of PD-1 on CD8+ T cells in NA treatment group.ConclusionThe acquired cellular immune in patients with chronic hepatitis B after NA treatment was not improved.The immune function of total CD4+ and CD8+ T cells in NA treatment group was lower than that in the immune control of CHB group.The level of serum HBsAg titer in NA treatment group was correlated with the frequency of Treg cells and inhibitory molecules on T cells.The acquired cellular immune in patients with chronic hepatitis B(CHB)who are treated with nucleot(s)ide analogue and achieve HBV-DNA<1000 IU/ml,HBeAg disappearance and HBsAg <3000 IU/ml was not restored.