Changes of Treg cells, Th17 cells and Treg/Th17 cell-associated cytokines in the peripheral blood of patients with chronic hepatitis B before and after nucleos (t) ide analogues antivirus therapy
Objective To explore the relationship between the efficacy of nucleos （t） ide analogues antivirus therapy and changes of Treg ceils, Th17 cells and their associated cytokines in the peripheral blood of patients with CHB. Methods Forty-four CHB patients treated for 12 weeks were enrolled in this study. The frequencies of Treg ceils （CD4＋CD25highCD1271low T cells） and Thl7 cells （CD3＋CD8-IL-17＋ T cells） in the peripheral blood were assessed by flow cytometric analysis. Treg/Thl7 cell-associated cytokines IL- l0, TGF-β1, IL-17 and IL-23 levels were measured by enzyme-linked immunosorbent assay （ELISA）. The comparisons of overall means within groups and between before and after therapy were done by Mann-Whitney U test or Wilcoxon matched paired T test. Results In 14 complete-responders of 44 CHB patients, the frequencies of Treg cells, the levels of IL-10, TGF-I31 and IL-23 and Treg/Thl7 ratio were decreased signifi- cantly after nucleos（t） ide analogues antivirus therapy （Z=-2.691, -2. 417, -2. 237, -2.291, -2.291, both P〈0.05） , while the frequencies of Thl7 cells and the IL-17 levels were increased slightly. In 11 patrial-responders, the frequencies of Treg cells, the levels of IL-10, TGF-IM and IL-23 were decreased significantlv after nucleos（t）ide analomaes antivirus therapy （Z=-1. 988, -2. 934, -2.756, -2. 803, both P〈0.05） ; The frequencies of Thl7 cells and the IL-17 levels were increased slightly, while Treg/Th17 ratio was slightly decreased. In 15 non-responders, the frequencies of Treg cells, Thl7 cells, the levels of IL-10, TGF-~I, IL-17 and IL-23 and Treg/Thl7 ratio were not changed significantly after nucleos（t） ide analogues antivirus treatment. Either HBV DNA decrease at least 2 log copies/m1 or ALT normal, the frequencies of Treg ceils, the levels of IL-10, TGF-~I and IL-23 were decreased significantly （all P〈0.05）. The frequen- cies of Treg cells were positively correlated with HBV DNA and ALT, and the level of HBV DNA were corre- lated with ALT. Conclusion Treg and Thl7 cells and their associated cytokines were changed significantly before and after NA treatment. In CHB patients who have achieved response after NA therapy, the frequency of Treg cells, the levels of IL-10, TGF-~I and IL-23 and Treg/Thl7 ratio in the peripheral blood were de- creased, while Thl7 cells frequencies and IL-17 levels were increased. 
 
Key words: 
iChronic hepatitis B ;  Treg cells ;  Thl7 cells ;  Nucleos（t） analogues ;  Cytokines