Effect of antiviral treatment on expression of programmed death 1 and programmed death ligand 1 on peripheral T lymphocytes in patients with chronic hepatitis C / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the changes in programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) expression on peripheral blood T lymphocytes of patients with chronic hepatitis C (CHC) over the 24 weeks course of antiviral therapy.</p><p><b>METHODS</b>Twenty-four CHC patients administered 24 weeks of combination antiviral therapy with pegylated-interferon-alpha-2a (Peg-IFNa-2a) and ribavirin (RBV) were enrolled for study from the Nanjing Second Hospital between October 2008 and October 2011. Peripheral blood was collected before treatment initiation, at treatment weeks 4, 12 and 24, and post-treatment week 24 (to investigate sustained virologic response (SVR), and used to measure expression of PD-1 and PD-L1 on CD4+ and CD8+ T lymphocytes by flow cytometry, load of serum hepatitis C virus (HCV) RNA by real-time polymerase chain reaction, and level of serum alanine aminotransferase (ALT) by auto-biochemical analyzer. Intergroup differences were analyzed by the two-sample t-test, and the significance of differences between pre- and post-treatment measurements was determined by one-way or two-way repeated measurements analysis of variance tests.</p><p><b>RESULTS</b>At treatment week 4, 19 of the CHC patients were HCV RNA-negative. Among those patients the PD-1 expression on both T lymphocyte subsets showed a significant decrease from pre-treatment to post-treatment week 24 (CD4+ 18.6 +/- 6.1% vs. 10.3 +/- 7.7%, F = 12.406, P = 0.002; CD8+ 16.6 +/- 13.8% vs. 9.4 +/- 4.6%, F = 4.955, P = 0.039). However, the CD8+ lymphocyte subset showed significant increase in PD-L1 expression during treatment (pre-treatment 17.5 +/- 13.7% vs. treatment week 4 25.9 +/- 11.1%, F = 9.063, P less than 0.01; 12 29.6 +/- 15.1%, F = 8.365, P less than 0.01; 24 32.0 +/- 15.7%, F = 9.736, P less than 0.01). Among the five CHC patients showing HCV RNA-positivity at treatment week 4 there was only a significant difference observed in the increased expression of PD-L1 on CD8+ lymphocyte subset from pre-treatment to treatment week 24 (17.4 +/- 16.7% vs. 39.2 +/- 15.6%, F = 10.292, P = 0.033). Twenty of the CHC patients achieved SVR. among whom the PD-1 expression was significantly decreased during treatment on the CD4+ lymphocyte subset (pre-treatment 20.2 +/- 7.5% vs. treatment week 4 14.4 +/- 7.5%, F = 6.133, P less than 0.05; 12 14.0 +/- 6.9%, F = 5.541, P less than 0.05; 24 10.7 +/- 7.6%, F = 14.780, P less than 0.05) and on the CD8+ lymphocyte subset (pre-treatment 16.8 +/- 13.4% vs. treatment week 12 10.2 +/- 4.6%, F = 4.964, P less than 0.05; 24 10.1 +/- 4.9%, F = 4.613, P less than 0.05). Additionally, the PD-L1 expression was significantly increased during treatment on the CD8+ lymphocyte subset (pre-treatment 19.0 +/- 14.5% vs. treatment week 12 30.8 +/- 16.6%, F = 6.442, P = 0.020; 24 35.2 +/- 16.5%, F = 12.349, P = 0.002). Among the four CHC patients who relapsed there were no significant differences observed in the expressions of PD-1 or PD-L1 on the CD4+ or CD8+ T lymphocytes.</p><p><b>CONCLUSION</b>The standard Peg-IFNa-2a + RBV combination antiviral therapy reduces PD-1 expression on CD4+ and CD8+ T lymphocytes and increases PD-L1 expression on CD8+ T lymphocytes in peripheral blood. The clinical outcome of CHC patients may be related to the antiviral therapy-induced changes in expressions of PD-1 and PD-L1 on T lymphocytes.</p>