Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B

Abstract

Aim: to investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB).

Methods: twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density: 1.077 g/L, Pharmingen) at weeks 0, 4, 8, 12, and 24, respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay.

Results: the frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05), the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05), the level of Th1-type cytokines [interleukin (IL)-12, tumor necrosis factor-α, and IFN-γ] was higher, while that of Th2-type cytokines (IL-4, IL-6, and IL-10) was lower in responders than in non-responders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597, P = 0.04), while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545, P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%, negative predict value = 92%).

Conclusion: pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.

Figures

Figure 1

Frequency of hepatitis B virus epitope tetramer+/CD8+ T cell after pegylated interferon α-2b treatment. The frequency of hepatitis B virus (HBV) specific CD8+ T cells was increased connectively at weeks 4, 8, 12 and 24 after pegylated interferon α-2b treatment with no difference in frequency of HBV core specific CD8+ T cells and HBV env specific T cells.

Figure 2

No correlation between increased hepatitis B virus epitope-specific CD8+ T cells and treatment outcome. The frequency of hepatitis B virus (HBV) core or env epitope-specific CD8+ T cells was higher in non-responders (NR) than in responders (R).

Figure 3

Correlation between increased hepatitis B virus specific T cells and treatment response 24 wk after therapy. The frequency of hepatitis B virus (HBV) core epitope-specific CD8+ T cells at week 24 was higher in responders (R) than in non-responders (NR).

Figure 4

Level of cytokines after treatment. The levels of Th1-type cytokines [interleukin (IL)-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ] were higher, while the levels of Th2-type cytokines (IL-4, IL-6 and IL-10) were lower at week 48 after treatment.

Figure 5

Positive correlation between alanine aminotransferase and inducible protein-10 levels (r = 0.545, P = 0.005). ALT: Alanine aminotransferase; IP-10: Inducible protein-10.