Expression Profile Of Tim-3 On CD8~+T Induced By Peptides And γ-chain Cytokines In Patients And Carriers With Chronic Hepatitis B Viral Infection

Viral hepatitis B, referred to as hepatitis B, is one of the human infectious diseases infected with the hepatitis B virus. According to statistics, there are about 350 million people with the chronic hepatitis B virus(HBV) infection in the world and nearly 600,000 dead people caused by viral hepatitis related diseases each year. According to a latest epidemiological research of Chronic hepatitis B(CHB), Hepatitis B virus carrying rate was 7.18% in our country.The Pathological mechanism of CHB is not completely clear, but the study found that the chronic infection with the hepatitis B virus is a constant state of immune tolerance mainly induced by HBV, particularly associated with Cytotoxic T lymphocyte(CTL) low reaction condition and the depletion of functional. In the infection process of CHB, Gamma-Chain(γC) cytokines and T-cell immunoglobulin domain and mucin domain-containing molecule-3(Tim-3)which is a negative immunomodulatory molecules both played a certain regulating function in CD8+T lymphocytes immune regulation, which in turn to affect the body to kill and remove HBV.In this study, we detected the expression of Tim-3 on CD8+T lymphocytes, by stimulated the Peripheral blood mononuclear cells(PBMC) of the patients and carriers of CHB with γC cytokines and antigens and so on. We analysed the correlation between Tim-3 high expression and γC cytokines and antigens, to futher clarify the pathogenesis and lay the foundation looking for a better immune therapy of chronic hepatitis B. Aims:To analyse their influence on the Tim-3 expression, CD8+T cells of PBMC in patients and carriers with chronic hepatitis B infection were stimulated with γC cytokines and antigens and the expression of Tim-3 on CD8+T cells were detected. Method:1. 56 Asymptomatic HBV carriers, 114 patients with CHB who had not received the treatment and 50 healthy human were enrolled. The related clinical data were collected, such as ALT and HBV DNA. 2. The Peripheral blood mononuclear cells of patients with CHB and healthy people were obtained with the lymphocyte separation technique and frozen. 3. According to the group, PBMC were stimulated alone or in combination with antigens, peptides, γC cytokines, γC cytokines neutralizing antibody. The expression of Tim-3 on CD8+T cells was detected by flow cytometry. 4. To analyse the impact of γC cytokines and antigens on the Tim-3 expression on CD8+T cells. Results:1. The stimulation with HBV peptides and γC cytokines alone, in combination and collaborative with anti-CD3/CD28 can significantly enhance the Tim-3 expression on CD8+T cells of patients and carriers of CHB. The differences are statistically significant. 2. The Tim-3 expression positively correlated with the level of ALT. 3. The γC cytokines neutralizing antibody can reduce the expression of Tim-3. The differences are no statistically significant. Conclusion:The results above reveal that the Tim-3 high expression on CD8+T cells of PBMC in CHB infection can be significantly induced not only by HBV Ag, HBV peptides and γC cytokine alone, but also by their combined stimulation. To futher clarify the pathogenesis of chronic hepatitis B.