Study On Characteristics Of Tfh Cells In Patients With Chronic Hepatitis B Virus Infection And Its Correlation With Treg And Tc Cells

Objective:To detect the levels of blood CD4+CXCR5+Tfh cells, CD4+CD25+FoxP3+Treg cells and CD3+CD8+Tc cells and investigate the possible association among the three cells in patients with chronic hepatitis B virus (HBV) infection.Methods:Fresh peripheral blood samples were collected from15chronic asymptomatic HBV carriers (AsC),42chronic hepatitis B (CHB) patients of whom25were seropositive for HBeAg and17were seronegative,11inactive HBsAg carriers (InC) and15healthy controls. The levels of CD4+CXCR5+Tfh cells, CD4+CD25+FoxP3+Treg cells and CD3+CD8+Tc cells were measured by flow cytometry.Results:1. The percentage of CD4+CXCR5+Tfh cells isolated from the AsC, HBeAg(+)CHB and HBeAg(-)CHB group were significantly higher than that in the HC group.17.66(15.34-20.56)%,21.95(19.60-26.32)%,22.33(17.58-24.85)%vs13.67(9.80-15.32)%respectively.(P<0.001). The levels of CD4+CXCR5+Tfh cells in the HBeAg(+)CHB or the HBeAg(-)CHB group was elevated significantly compared to that in the AsC or the InC [16.11(12.33-19.73)%] group.(P<0.05).2. A negative correlation was found between the circulating CD4+CXCR5+Tfh cells and the HBV DNA load (r=-0.275, P<0.05), while no significant relationship was found between the circulating CD4+CXCR5+Tfh cells and the ALT or HBsAg levels.3. The levels of CD4+CD25+FoxP3+Treg cells in the AsC group was significantly higher than that in the HC group [7.70(6.35-9.13)%vs6.53(5.54-7.35)%, P<0.05]. Meanwhile, there was a decreasing tendency of the levels of CD4+CD25+FoxP3+Treg cells in the HBeAg(+)CHB [7.52(6.09-8.49)%] group compared to the AsC group.4. There was no correlation between the circulating CD4TCD25+FoxP3+Treg cells and the HBV DNA load. In the AsC group, a positive relationship was found between the circulating CD4+D25+FoxP3+Treg cells and the HBV DNA load (r=-0.275. P=0.041), while no significant relationship was found in the HBeAg(+) or HBeAg(-)CHB group.5. Compared to the HC group, the frequency of blood CD3+CD8+Tc cells in the AsC HBeAg(+)CHB, HBeAg(-)CHB and InC group was on a decreasing tendency (P>0.05). A reduced trend was aslo found in the HBeAg(+)CHB or HBeAg(-)CHB group compared with the AsC group (P>0.05).6. In patients with chronic HBV infection, there was no significant relationship between CD4+CXCR5+Tfh cells and CD4+CD25+FoxP3+Treg cells or CD3+CD8+Tc cells. In the HBeAg(+)CHB group, a positive relationship was found between the circulating CD4TCXCR5+Tfh cells and CD3+CD8+Tc cells (r=0.466, P=0.019). In the other groups no significant relationship was found among the three cells.Conclusions:CD4+CXCR5+Tfh cells may participate in the chronic HBV-related immune response, and the skewing between CD4+CD25+FoxP3+Treg cells and CD4+CXCR5+Tfh cells may correlate with disease activity.