The Expression And Significance Of FoxP3~+Tregs And IL-17~+T Cells In The Liver Tissue Of Patients With Chronic HBV Infection

BackgroundCD4~+T lymphocytes and CD8~+T lymphocytes contribute to the HBV remove. Both T helper cell 17(Th17) and regulatory T cells(Tregs) belong to the CD4~+T family. Th17 and Tregs play an important role in autoimmune diseases and the process of body defense. And the abnormal expression or function of Th17 or Tregs will contribute to the occurrence of autoimmune diseases. In short, both the Th17 and Tregs have the function of immune regulation, closely related to many immune diseases, for example rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis and so on. And reports showed that both Th17 and Tregs were involved in the progression of acute hepatitis B, chronic hepatitis B, HBV-associated liver cirrhosis, HBV-associated liver failure and hepatocellular carcinoma based on HBV. The change of frequency and function of the both cells may influence the prognosis of the HBV-associated liver diseases. As we all known, the process of chronic HBV infection is generally divided into 4 phases, immune tolerance, immune clearance phase, low copy phase and active period, based on the different biochemistry index and histopathology situation which is important to the treatment and the assess of prognosis for patients with chronic HBV infection. Now there were some studies about the expression level of CD4~+T and CD8~+T cells in the patients who were at the different phases of chronic HBV infection, and these studies based on the patients’ peripheral blood in general, however only depending on simple peripheral blood assay index is not enough to accurately monitor the patients’ liver condition. Those studies based on the liver tissue of patients with chronic HBV infection just going on in the patients who at the stage of immune tolerance and immune clearance. But the studies about the 4 stages, immune tolerance, immune clearance phase, low copy phase and active period were few, not to mention the studies based on the liver tissue. So our study not only detect the CD4~+T, CD8~+T, Fox P3~+Tregs and IL-17~+T cells in the liver tissues of the patients with chronic HBV infection, but also compare the expression level of these cells in the immune tolerance, immune clearance phase, low copy phase and active period phase respectively.Objective1. Observing the expression level of Fox P3~+Tregs, IL-17~+T, CD4~+T and CD8~+T, cells in the liver tissue of patients with chronic HBV infection and comparing with the healthy controls.2. Analyzing the relationship between Fox P3~+Tregs, IL-17~+T cells and the clinical indexes in the chronic HBV infection.3. Comparing the expression level of Fox P3~+Tregs, IL-17~+T, CD4~+T and CD8~+T cells in the liver tissues of patients in immune tolerance, immune clearance phase, low copy phase and active period and discussing if they have clinical significance.MethodThe level of FoxP3~+Tregs, IL-17~+T, CD4~+T and CD8~+T cells were detected by the method of immunohistochemistry in 71 chronic HBV infection, including 29 patients with chronic hepatitis B, 42 patients with HBV-related cirrhosis; then comparing with 34 individuals without HBV infection as health controls. All the section from liver tissues by serial section technique.Results1.Compared with the healthy control group, the Fox P3~+Tregs, IL-17~+T, CD4~+T and CD8~+T cells in the liver tissues of patients with chronic hepatitis B and HBV-related cirrhosis were significantly higher, P<0.01; and there are no difference between the chronic hepatitis B group and HBV-related cirrhosis group.2.When the inflammation stage of liver tissues increase, the level of expression of IL-17~+T cells in the liver tissues of chronic HBV infection will increase in some extent(G3-G4 vs G1-G2, P=0.053).3.There are a positive correlation between Fox P3~+Tregs and AST in the chronic HBV infection(r=0.382, P=0.028). Moreover the level of expression of Fox P3~+Tregs increasing with CD8~+T cells in the chronic HBV infection(P<0.001).4.The level of expression of IL-17~+T cells in the immune tolerance, immune clearance phase, low copy phase and active period were almost, P>0.05, as well as Fox P3~+Tregs, CD4~+T and CD8~+T cells.Conclusion1. We confirmed that IL-17~+T cells were related to the chronic HBV infection again.2. We found that maybe the Fox P3~+Tregs can act as an alarm device for the liver injures of chronic HBV infection.3. We found that now there were no clear relation between the natural history of chronic hepatitis B with the expression level of Fox P3~+Tregs and IL-17~+T cells.4. The study showed us that the expression level of the trend of CD4~+T and CD8~+T cells in the immune tolerance, immune clearance phase, low copy phase and active period can reflex the immune status of every period in some extent.