A novel evaluation system for T lymphocytes immune function based on the expression of co-stimulatory molecules in chronic HBV-infected patients

Objective To investigate the expression and significance of CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1) and T cell immunoglobulin mucin-3 (Tim-3) on T lymphocytes in chronic HBV-infected patients. Methods A total of 102 chronic HBV-infected patients, including 42 patients with chronic hepatitis B (CHB), 30 patients with hepatitis B-induced liver cirrhosis (LC), and 30 patients with hepatocellular carcinoma (HCC), were enrolled from the First Affiliated Hospital to Soochow University during October 2012 and June 2013. Thirty healthy individuals were also enrolled as controls. Expression of CD28, CTLA-4, PD-1, Tim-3 on T lymphocytes in peripheral blood were determined by flow cytometry, and the differences among groups were analyzed using one-way ANOVA and LSD-t test. Spearman correlation test was performed to analyze the correlations of the expression of CD28, CTLA-4, PD-1, Tim-3 on T lymphocytes with HBV DNA loads, HBeAg and ALT. Results The expression of CD4+ CD28+ , CD8+ CD28+ , CD4+ CTLA-4+ in chronic HBV-infected patients were lower than those in healthy controls. CD4+ CD28+ expression in HCC group was lower than that in CHB group (t=2.373, P<0.05); CD8+ CD28+ expression in LC and HCC group was lower than that in CHB group (t=4.324 and 4.088, P<0.01); CD8+ PD-1+ , CD4+ Tim-3+ and CD8+ Tim-3+ expressions in CHB group were higher than those in LC, HCC group and healthy controls (t=3.051, 3.130, 3.121, 3.254 and 3.723, P<0.01). CD8+ PD-1+ expression was positively correlated with ALT levels and HBV DNA loads (r=0.516 and 0.582, P<0.01); CD8+ Tim-3+ expression was also positively correlated with ALT levels and HBV DNA loads (r=0.578 and 0.556, P<0.01); PD-1 and Tim-3 expressions on CD8 T lymphocytes were positively correlated with each other(r=0.578, P<0.01). Conclusion The abnormal expression of the molecules on T lymphocytes in chronic HBV-infected patients is closely correlated with immune function disorder and the progression of the disease. Key words: Hepatitis B virus; T-lymphocytes; CD28; Cytotoxic T-lymphocyte antigen-4; Programmed death-1; T cell immunoglobulin and mucin domain-containing protein 3