Investigation of Regulatory T Cells and Secreted Immunomodulatory Cytokine IL-10 Levels in Patients with Hepatitis B

Abstract

Hepatitis B infection is still among the most important public health problems worldwide, even great improvements have been made in the treatment strategies. Hepatitis B virus (HBV) replicates itself by entering the liver cells and simultaneously with the antigen release, many antagonistic immune responses are induced by the regulatory cells including T cell (Treg), T helper 17 (Th-17), T helper 1 (Th-1) and T helper 2 (Th-2) cells. The main function of Treg cells is to develop an appropriate immune response against infection and to suppress the immune response if it is not required. Tregs suppress the effector T cells via secreting immune system supressor cytokines such as Transforming Growth Factor-Beta and interleukin (IL)-10 or contact dependent way. Tregs protect cells from immunopathologic damage of HBV specific T cell immune response and also cause viral persistence, cirrhosis, hepatocellular carsinoma (HCC) and autoimmunity but the mechanisms are not clear, yet. In this study, we aimed to determine whether evaluation of Treg cells and cytokine IL-10 levels together in hepatitis B patients is useful that may indicate the disease survey and response to the treatment. The peripheral blood samples of ninety-one volunteers, including 61 HBV infected patients and 30 healthy controls selected from applicants of Infectious Diseases Outpatient/Clinic Service, were taken. Their CD4(+)CD25(high)FOXP3(+)CD152(+)CD127(low) Treg cell distribution were measured by flow cytometry method, using the recently defined markers. The level of IL-10 cytokine released by immunomodulatory cells was determined by quantitative ELISA method. Treg cell percentages of the patients with acute hepatitis B were below the normal range (2-4%) (median=1.50%, 0.6-3.5) and the difference was statistically significant (p=0.005). Treg cell percentages of the patients with chronic hepatitis B were higher than the control group (p<0.05), and it was found to be related to the parameters used in the diagnosis, staging and follow-up of the disease. IL-10 levels were significantly higher in all hepatitis B clinical stages compared to the healthy controls (median=11.7, 17.3-44.9) (p<0.05). Also, in parallel with Treg cells, IL-10 levels were correlated with HBV DNA load and HBsAg levels (r=0.48, p<0.02). Treg cells and the related cytokine IL-10 are thought to play an important role in the immunology of HBV infection and therefore, promising to follow up the disease and to develop new therapeutic strategies targeting the Treg cell.