Study of liver-targeted regulatory T cells in hepatitis B and C virus in chronically infected patients

Abstract

Introduction: Regulatory T cells (Tregs) play a critical role in chronic viral infections. The role of Tregs in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) is unknown. This study examined the distribution and frequency of forkhead box p3+ (Foxp3+) Tregs in the liver tissue and compared the clinicopathological characteristics of CHB and CHC patients. Methods: Liver needle biopsies were obtained from 26 patients who were hepatitis B surface antigen positive and 27 patients who were hepatitis C virus antibody positive. Results: The ratio of Foxp3+ Tregs in CD3+ T cells was similar in HBV and in HCV cases. In HBV cases, the variables that were positively associated with the ratio of Foxp3+ Tregs in CD3+ T cells included the serum alanine aminotransferase level (R = 0.402, P = 0.025) and the ratio of CD8+ T cell plus CD56+ NK cell against CD4+ T cell (R = 0.53, P = 0.005). The ratio of Foxp3+ Tregs in CD3+ T cells increased more in the severe activity group than in the mild activity group (P = 0.04). In HCV cases, the ratio of Foxp3+ Tregs in CD3+ T cells increased significantly in terms of the genotype2 (P = 0.0002) and male gender (P = 0.04). In addition, the ratio of Foxp3+ Tregs in CD3+ T cells showed a negative correlation with the ratio of CD8+ T cell plus CD56+ NK cell against CD4+ T cell (R = -0.508, P = 0.005) and HCV viral load (R = -0.482, P = 0.001). Conclusions: Liver-targeted regulatory T cells present similarly in CHB and CHC, but their relationship with the effector cell population, the inflammation grade or the viral load is different between CHB and CHC. © 2009 John Wiley & Sons A/S.