The role of intrahepatic regulatory T cells/helper thymphorytes 17 balance in patients with different phases of chronic hepatitis B virus infection / 中华传染病杂志

ABSTRACT

Objective To analyze the change of intrahepatic regulatory T cells (Treg )/helper thymphorytes (Th)17 balance in patients with different phases of chronic hepatitis B virus (HBV ) infection ,and to explore the role of Treg/Th17 balance in maintaining immune tolerance and inducing immune clearance ,and its influence on disease progression .Methods Sixty-eight patients with chronic HBV infection who underwent liver biopsy in Tianjin Second People′s Hospital were included .The 68 patients included 20 cases in immune tolerant (IT) phase ,36 cases in immune clearance (IC) phase and 12 cases in inactive phase .Eight healthy liver transplant donors were collected as healthy controls .The intrahepatic Treg/Th17 levels were detected by immuno-histochemical method . The changes of Treg/Th17 balance in patients with different phases of chronic HBV infection ,and the relationship between Treg/Th17 balance and the decreases of hepatitis B surface antigen (HBsAg ) , hepatitis B antigen (HBeAg) and HBV DNA levels in the peripheral blood were analyzed in patients with IC phase at two weeks of admission .Results The intrahepatic Treg and Th17 levels in IC phase group were the highest , then and they were higher in inactive phase group were higher than those in IT phase group ,And they were the lowest in control group .The Treg level in IC phase group increased significantly compared with the other three groups (all P< 0 .01) ,and there were no significant differences among the other three groups (all P> 0 .05) .The Th17 level between IT phase group and inactive phase group was not significantly different (P> 0 .05) ,while the differences were not significant in other groups (all P>0 .05) .Treg/Th17 ratio of IT phase group was the highest ,then the ratio of control group was higher than that of inactive phase group ,and IC phase group was the lowest ratio .The differences between IC phase group ,control group and IT phase group were significant (all P< 0 .05) ,and the difference between inactive phase group and IT phase group was also significant (all P<0 .05);and there was no significant difference among other groups (all P>0 .05) .The decreases of HBsAg ,HBeAg and HBV DNA levels in the peripheral blood at two weeks admission were negatively correlated with the intrahepatic Treg cell level in patients in IC phase of chronic HBV infection ( r= -0 .941 ,-0 .869 ,and -0 .883 ,respectively ,both P<0 .01) .The Treg ,Th17 levels and their ratio in IC phase group with different degree of inflammation and fibrosis had significant differences :G4 group > G3 group > G2 group ,S3 group > S2 group > S1 group (all P<0 .05) .Conclusions There is no change of the Treg/Th17 balance in IT phase ,and Treg has no influence on maintaining immune tolerance in chronic HBV infection .T he imbalance of Treg/Th17 is observed in IC phase .Th17 may actively participate in the immune-mediated liver injury and the development of hepatic fibrosis in CHB patients .Treg may inhibit inflammation and reduce liver injury via the negative feedback regulation mechanism ,and may impede the eradication of HBV simultaneously .