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

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.