Significance Of CD4~+CD25~+Foxp3~+Regulatory T Cells,CD3~-CD16~+CD56~+NK Cells And CD3~+CD16~+CD56~+NKT Cells In Peripheral Venous Blood Of Children With Chronic Hepatitis B Virus Infection

Aims:The cellular immune mechanism of chronic hepatitis B (CHB) is not fullly understood. The roles of the CD4+CD25+Foxp3+regulatory T cells (Treg), CD3CD16+CD56+NK cells and CD3+CD16+CD56+NKT cells, and the potential relationship in pediatric subjects of Asymptomatic HBV carriers (AsC) and CHB should be explored.Methods:Fresh peripheral venous blood samples were obtained from39cases of AsC,22cases of CHB and34healthy controls. The number and distribution of CD4+CD25+Foxp3+Treg cells, CD3-CD16+CD56+NK cells and CD3+CD16+CD56+NKT cells were analyzed by flow cytometry. Liver function (including ALT, AST, Tbil), HBVM (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, PreS, PreS1IgM) and HBV DNA level with a low detection limit of500viral genome copies/ml were determined for each patient.Results:the ratio of CD4+CD25+Foxp3+Treg cells in peripheral venous blood of children with CHB were higher significantly than those of normal control and AsC (P=0.000,P=0.009), and the frequency was positively correlated with total serum bilirubin (Tbil)(r=0.490,P=0.000). The frequencies of CD3-CD16+CD56+NK cells and CD3+CD16+CD56+NKT cells in CHB group were significantly lower than those of healthy control (P=0.002,P=0.028) and AsC (P=0.046, P=0.002). In CHB group, the frequency of CD3-CD16+CD56+NK cells was negatively correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)(r=-0.286and-0.299,P=0.025and0.019, respectively), and the frequency of CD3+CD16+CD56+NKT cells was negatively correlated with Tbil (r=-0.324,P=0.011). There was no statistically difference between AsC and healthy controls in frequencies of CD4+CD25+Foxp3+Treg cells, CD3-CD16+CD56+NK cells and CD3+CD16+CD56+NKT cells (P=0.110,0.153,0.495, respectively). There’s no relationship between the frequencies of CD4+CD25+Foxp3+Treg cells and CD3-CD16+CD56+NK cells, CD3+CD16+CD56+NKT cells. The frequencies of CD4+CD25+Foxp3+Treg cells, CD3-CD16+CD56+NK cells and CD3+CD16+CD56+NKT cells had no corresponding with HBV DNA level or HBeAg status.Conclusions:Children with CHB exhibite significantly high frequency of CD4+CD25+Foxp3+Treg cells, and low frequencies of CD3-CD16+CD56+NK cells and CD3+CD16+CD56+NKT cells. CD4+CD25+Foxp3+Treg cells, CD3-CD16+CD56+NK cells and CD3+CD16+CD56+NKT cells are potentially involved in the immune tolerance in HBV infected-children and chronicity of hepatitis B.