| Objective To analyze the expression of CD28,CTLA-4, PD-1,Tim-3on T cells andthe levels of IL-4、IL-6、IFN-γin the plasma with HBV chronic patients. In attempt toinvestigate the correlation of peripheral T-cell immune function and chronic hepatitis Bvirus.Methods First part The levels of CD28,CTLA-4, PD-1, Tim-3on T cells and theabsolute value of T lymphocyte subsets were determined by Flow Cytometry, including42cases chronic hepatitis B (CHB),30cases cirrhosis(LC),30cases primary livercancer(HCC) and30cases normal control(NC). The load of HBV DNA in serum wasdetected by Real-time PCR and the serology markers such as HBeAg and ALT weredetected by conventional methods.Second part The levels of IL-4、IL-6、IFN-γin the plasma were determined by ELISA,including42cases chronic hepatitis B (CHB),30cases cirrhosis(LC),30cases primaryliver cancer(HCC) and30cases health control(NC). The load of HBV DNA in serum wasdetected by Real-time PCR and the serology markers such as HBeAg and ALT weredetected by conventional methods.Results First part There were statistically significant difference with the expressionlevels of CD4+CD28+(H=34.358,P<0.001) in different groups, with the highest expressionlevel in the NC group[1213.95(994.95～1608.27)]and the lowest expression in LCgroup[542.91(316.53～884.85)]. There were statistically significant difference with theexpression levels of CD8+CD28(H=37.229,P<0.001) in different groups, with the highestexpression level in the CHB group[355.29(195.93～503.37)] and the lowest expression inLC group[122.37(57.51～207.48)]. There were statistically significant difference with the expression levels of CD4+CTLA-4+(H=23.765,P<0.001), with the highest expression levelin the NC group[653.7(527.91～757.44)] and the lowest expression in LC group[204.06(90.69～411.27)]. There were statistically significant difference with the expression levelsof CD8+PD-1+(H=12.055,P=0.007), with the highest expression level in CHBgroup[18.06(4.14～36.21)] and the lowest expression in LC group[4.47(2.16～10.68)].There were statistically significant difference with the expression levels ofCD4+Tim-3+(H=9.480,P=0.024), with the highest expression level in CHB group [380.64(123.48～723.75)] and the lowest expression in LC group[145.95(78.33～272.73)]. Therewere statistically significant difference with the expression levels ofCD8+Tim-3+(H=33.647,P<0.001), with the highest expression level in CHBgroup[145.95(78.33～272.73)] and the lowest expression in HCC group[8.31(3.69～12.96)]. There were significant positive correlation of the expression level of PD-1on CD8T cell and the level of ALT(r=0.690,P<0.01), and HBV DNA load(r=0.730,P<0.01). Therewas significant and positive correlation of the expression level of Tim-3on CD8T cell andHBV DNA load(r=0.578,P<0.01), and the expression level of PD-1on CD8Tcell(r=0.363,P<0.01).Second part There were statistically significant differences with the expression levelsof IL-4,IL-6and IFN-γ in the researched groups. The expression levels of these threemolecules in CHB, LC and HCC groups were significantly higher than NC group. Theexpression level of IL-4in the CHB group was significantly higher than LC and HCCgroups. The expression level of IL-6in the HCC group was significantly higher than CHBand LC groups. Compared with the NC group, the ratio of IFN-γ/IL-4in CHB, LC andHCC groups were significantly decreased. There was significantly positive correlationbetween the level of IL-4with the load of HBV DNA (r=0.757, P<0.001). The level ofIFN-γ had significantly negative correlation with the load of HBV DNA(r=-0.786,P<0.001)and the level of ALT(r=-0.713,P<0.001). The cytokines in the serum of patients withchronic HBV had no significant correlation of the HBeAg concentration. Conclusion1. The expression levels of CD28, CTLA-4, PD-1, Tim-3on T cells showed differentdegree of change, especially PD-1and Tim-3had different degrees of correlation withHBVDNA load and ALT concentrations. The abnormal expression levels of CD28, CTLA-4,PD-1and Tim-3, especially PD-1and Tim-3may be present in the process of chronic HBV.Therefore, monitoring their levels may reflect the T cell immune function in patients.2. The results showed cytokines in plasma dominant Th2-type cells exist in a state ofchronic HBV patients, that would provide a good basis on treatment and the efficacyobservation of diseases. IL-6levels were significantly higher in HCC group, whichprovided some clues for the next study of the pathogenesis of liver cancer.3. Some costimulatory molecules on T cells and cytokines in plasma combinedabsolute analysis of T lymphocyte subsets may be able to reflect T cell immune functionwith the HBV chronic patients. Parallel analysis indicators HBV DNA load and ALT canbe used as the reflection of immune function, in order to facilitate understanding of theirHBV infection status and liver function. |
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