| Objective: An estimated80%of people who acquire HCV infectionprogress to development of persistent of chronic HCV infection. Themechanisms responsible for the persistent HCV infection are not clear. Thelack of HCV-specific CD4~+T and CD8~+T cell immune response may be one ofthe important factors. Programmed Death-1(PD-1) is a negativeco-stimulatory molecule expressed on T cells and B cells which can negativelyregulate the immune responses. By interacting with its cognate ligands PD-L1or PD-L2, PD-1can weaken, limit and terminate function of T cells. Therewere studies observed peripheral blood T-cell depletion and higher intensity ofprogrammed death-1expression on T cells in patients with HCV infection.The dynamic changes in T cell subsets and programmed death-1expression inchronic hepatitis C patients undergoing pegylated-interferon and ribavirintherapy has not yet been reported. This study aimed to investigate the dynamicchanges in T cell subsets and programmed death1expression during antiviraltreatment of chronic hepatitis C patients.Methods: All of the25subjects meeting guidelines for antiviral therapyincluding11male patients and14female patients didn't receive antiviral andregulated immunity therapy within6months before this study. All patientsused peg-interferon and ribavirin antiviral therapy, and grouping for0,4,12,24and48week group.10healthy persons were enrolled in this study.1Fresh anti-freezing peripheral blood was collected from all of the subjects.PBMC was isolated by density gradient centrifugation. The PBMC wasstained with anti-CD3-ECD, anti-CD4-FITC, anti-CD8-PE-Cy5, anti-PD-1-PEand the expression density of PD-1, CD4~+T and CD8~+T were detected by flowcytometric analysis.2Fresh peripheral blood was collected from all of the subjects. PBMC was isolated by density gradient centrifugation. The expression levels ofPD-1mRNA were detected using reverse transcription-polymerase chainreaction (RT-PCR).Results:1Clinical outcome: in all patients,18(72%) achieved RVR;5(20%) achievedEVR;2(8%) achieved PVR;25(100%) achieved ETVR.2During antiviral treatment, the expression levels of T cell subsets in chronichepatitis C patients changed as follows: compared with those of normalcontrols, the expression levels of CD4~+T were higher, the expression levels ofCD8~+T were lower, the ratios of CD4~+/CD8~+were higher, in addition to the48week group was no statistical significance, the other groups are statisticallysignificant(P＜0.01); After peg-interferon and ribavirin treatment, comparedwith the0week group, the expression levels of CD4~+T decreased gradually, inaddition to the4week group was no statistical significance, the other groupsare statistically significant(P＜0.01); the expression levels of CD8~+Tincreased gradually(P＜0.01); the ratios of CD4~+/CD8~+decreased gradually(P＜0.01).3During antiviral treatment, the expression density of PD-1on CD4~+T inchronic hepatitis C patients changed as follow: the expression density of PD-1on CD4~+T cell (0week-48week group:8.95±1.55,6.53±1.06,6.42±0.87,5.12±0.58,4.42±0.58) was significantly higher than those of normal controls(2.92±0.87)(P＜0.01); after peg-interferon and ribavirin treatment, comparedwith the0week group, the expression density of PD-1on CD4~+T celldecreased gradually (P＜0.01).4During antiviral treatment, the expression density of PD-1on CD8~+T inchronic hepatitis C patients changed as follow: the expression density of PD-1on CD8~+T (0week-48week group:5.12±0.87,3.52±0.58,2.62±0.58,1.81±0.29,1.51±0.39) were significantly higher than those of normalcontrols(1.11±0.39)(P＜0.01); after peg-interferon and ribavirin treatment,compared with the0week group, the expression density of PD-1on CD8~+Tdecreased gradually (P＜0.01). 5According to the reverse transcription-polymerase chain reaction (RT-PCR)tests,the PD-1-mRNA expression levels on PBMC(0week-48week group:1.48±0.09,1.36±0.02,1.19±0.01,1.02±0.01,0.82±0.03),compared with thoseof normal controls(0.81±0.01)increased significantly. After the peg-interferonand ribavirin treatment, the PD-1-mRNA expression levels on PBMCdecreased gradually(P＜0.05or＜0.01).Conclusion:1The T cell subsets are imbalance in Patients with chronic hepatitis C virusinfection, Antiviral treatment can make imbalanced T cell subsets tends to benormal, suggesting that the imbalance of T lymphocytes are closed related tochronic HCV infection, T lymphocytes play an important role in clearingHCV infection.2The expression density of PD-1on CD4~+and CD8~+T cell and PD-1mRNAon PBMC in chronic hepatitis C patients was higher than the normal control,and decreased gradually with the extension of antiviral time and HCV-RNAreduction. It pointed out higher expression intensity of PD-1may associatedwith the replication of HCV-RNA. CHC improved accompany with thedecrease of expression density of PD-1, which pointed out that PD-1expression could predict the CHC efficacy. |
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