CD4+CD25+Foxp3+ Regulatory T Cells Contribute in Liver Fibrosis Improvement with Interferon Alpha

Abstract

The aim of this study is to investigate the optimal dose, treatment time, and possible immunologic mechanisms of interferon alpha (IFN-α) in the treatment of liver fibrosis. Mice were injected intraperitoneally with 10 % carbon tetrachloride to induce liver fibrosis, except in the normal control group. The experimental mice were randomly divided into four groups: physiological saline group, 20 U/gb wt IFN-α group, 40 U/gb wt IFN-α group, and 60 U/gb wt IFN-α group. After 3 and 6 weeks, type I collagen was detected in liver by hematoxylin and eosin (HE) stain, Masson's trichrome stain, and immunohistochemical staining. The number of CD8(+) T cells, the number of CD4(+)CD25(+)Foxp3(+) Tregs and the activation of CD4(+) T cells were detected in liver and spleen. Beneficial effects were observed in the 40 U/gb wt IFN-α group by pathological analysis. The number of CD8(+) T cells in the liver was significantly lower in mice receiving middle-dose IFN-α therapy as compared to mice receiving physiological saline (P < 0.05), while CD4(+)CD25(+)Foxp3(+) Tregs and activation of CD4(+) T cells in the liver were significantly higher in the therapeutic group than in the physiological saline group (P < 0.05). CD8(+) T cells (r = 0.3796) and activated CD4(+) T cells (r = 0.2437) were found to be positively correlated with the degree of liver fibrosis. CD4(+)CD25(+)Foxp3(+) Tregs (r = -0.7932) was found to be negatively correlated with the degree of liver fibrosis. IFN-α can inhibit liver fibrosis following 6 weeks of middle-dose IFN-α therapy by upregulating CD4(+)CD25(+)Foxp3(+) Tregs and suppressing CD8(+) T cells.