Founction And Clinical Significance Of Treg Cells In Patients With HCV Infection

Objective Hepatitis C virus(HCV) is one of the causes of chronic liver disease, and HCV infection results in the development of chronic liver diseases such as cirrhosis and hepatocellular carcinoma. One of the reasons for the high rates of chronic HCV infection is immunosuppression, which may be specifically mediated by the regulatory T-cells(Treg cells). The accumulation of Treg cells plays a pivotal role in suppressing the antiviral effector T-cells that are essential for viral clearance. Recently, a growing body of evidence has indicated that Treg cells may contribute critically to the induction of immune tolerance and affect the proliferation, differentiation, and cytokine secretion of HCV-specific lymphocytes. In this study, we enrolled the the peripheral blood from HCV patients, detected the expression of CD39, CD73 and TGF-b on Treg cells and three subsets; in addition, the percentage of Treg cells and three subsets were examined; finally, To prove that the antiviral therapy was effective, the percentages of CD4+Foxp3+ total Treg cells and three subsets of Treg cells were compared between patients with a SVR and those without a SVR.One hundred and forty-five subjects were enrolled in this study and divided into two groups: CHC patients(n = 105) and healthy donors(n = 40). The 105 CHC patients were hospitalized during the period January 2011 to January 2015 in the First Affiliated Hospital of Zhengzhou University. We obtained the peripheral blood mononuclear cells using the Ficoll-Plaque and restored in-80°C fridge for use nextly. The expression of inhibitory molecular CD39, CD73 and TGF-b and the percentage of Treg cells were detected by flow cytometry. Peripheral blood mononuclear cells were collected from the naive patients who had not undergone any previous treatment in order to evaluate the effect of IFN-a and RBV, for example the changes of CD39, CD73 and TGF-b(11) on Treg cells in vitro. MethodsResults 1. Compared with healthy dornor, total Treg cells, r Treg cells and a Treg cells in HCV patients all showed high tendency, but there was no difference on the percentage of non-Treg cells. 2. Compared with non-Treg and r Treg cells, a Treg cells expressed higher levels of ectonucleotidase, such as CD39 and CD73, and inhibitory cytokine TGF-b(26) The expression of CD39, CD73, and TGF-b on CD8+ T-cells and CD4+CD25- T-cells from HCV-infected patients and healthy donors was also examined. Compared with healthy donors, HCV-infected patients had a higher expression of CD39, CD73, and TGF-b on these cells. 3. In patients with genotype 1b and 2a, total Treg cells, r Treg cells and n Treg cells, except for non-Treg cells, decreased during the antiviral therapy. 4. After treatment with interferon alpha(IFN-a) and ribavirin(RBV) in vitro, the frequencies of total Treg cells, a Treg cells, non-Treg cells and r Treg cells in peripheral blood mononuclear cells, as well as the levels of transforming growth factor beta(TGF-b) secreted by a Treg and non-Treg cells, were significantly decreased. In addition, we also found purified Treg cells expressed lower levels of CD73 and TGF-b after treated with IFN-a and RBV. 5. The percentages of total Treg cells and a Treg cells were found to be much lower in patients with a SVR than in relapsed patients.Conclusion a Treg cells from patients infected HCV highly express CD39, CD73 and TGF-?(11) and compared with patients without SVR, a Treg cells exhibit lower percentage in patients with SVR, suggesting that a high frequency of a Treg cells might be associated with a poor clinical outcome in HCV infection.