Dynamic analysis of CD127 expression on memory CD8 T cells from patients with chronic hepatitis B during telbivudine treatment

Abstract

Background: Accumulating evidence supports the theory that expression of CD127 on CD8 T cells during the process of antiviral immune response indicates a subset of effect CD8 T cells that successfully develop into fully protective memory. CD8 T cells expression of CD127 may be used as a predictor to evaluate disease status in chronic viral infection. The aim of this study was to investigate the CD127 expression level on different subsets of CD8 T cell and explore the relationship between CD127 expression on CD8 memory T cells and serum hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) levels in patients with chronic hepatitis B (CHB). We also aimed to investigate the CD127 expression pattern on CD8 memory T cells of CHB patients who were treated with Telbivudine.

Methods/results: Twenty HBeAg-positive CHB patients were selected and treated with telbivudine 600 mg/day for 48 weeks. The memory CD8 T cells were characterized by expression of CD45RA and CD27 markers. CD127 expression on the CD8 T-cell surface was measured by four-colour flow cytometry. Our results showed that CD127 expression on memory CD8 T cells was reduced in CHB patients. There was a strong negative correlation between CD127 expression on memory CD8 T cells and serum HBV DNA and HBeAg levels in CHB patients. Moreover, successful antiviral therapy increased CD127 expression on CD8 memory T cells as well as on HBV-specific CD8 T cells in CHB patients.

Conclusion: These results suggest that diminished CD127 expression on CD8 memory T cells of CHB patients is a potential mechanism explaining cellular immune function impairment in CHB infection, and that CD127 expression on CD8 memory T cells is a useful indicator for evaluating the effects of anti-HBV therapy.

Figure 1

Ex vivo expression of CD127 by memory CD8 T cells taken from chronic hepatitis B (CHB) patients. (a) CD127 expression by CD27⁺CD45RA⁺ naive CD8 T cells. Results are shown for one healthy control and two CHB patients. (b) Proportion of CD127⁺ lymphocyte cells in the memory (CD45RA^-CD27⁺), effector (CD45RA^-CD27^-) and terminally differentiated effector (CD45RA⁺CD27^-) CD8 T-cell subsets in healthy controls and CHB patients (n = 20 for each group). Healthy controls (gray bar); CHB patients(black bar). *P < 0.05 when compared to healthy controls.

Figure 2

Decreased CD127 expression on memory CD8 T cells from chronic hepatitis B (CHB) patients. (a) Representative dot plots showing the expression of CD127 on CD8 T cells in one CHB patient and one healthy control. The numbers on the right indicate the percentages of CD8 T cells that are CD127⁺ and CD127^-. (b) Absolute counts per cubic millimetre of total CD127^- lymphocytes in naive, memory, effector and terminally differentiated CD8 lymphocytes from each study group. Healthy controls (gray bar); CHB patients(black bar). *P < 0.05 when compared to healthy controls.

Figure 3

The relationship between CD127 expression on memory CD8 T cells and serum hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) levels in chronic hepatitis B (CHB) patients. (a) Expansion of CD127⁺ memory CD8 T cells is correlated inversely with serum HBV DNA level in CHB patients. (b) Expansion of CD127⁺ memory CD8 T cells is correlated inversely with serum HBeAg level in CHB patients. All analyses were performed on the 20 CHB patients described in the Materials and Methods.

Figure 4

Antiviral therapy increases CD127 expression on CD8 memory T cells in chronic hepatitis B (CHB) patients. The mean expression of CD127 on CD8 memory T cells. The analysis was performed on 20 CHB patients treated with telbivudine at 0, 24 and 48 weeks. Statistical analyses were performed among 6 well responders (black bar), 10 partial responders (gray bar) and 4 non responders (white bar) (*P < 0.05).

Figure 5

The emergence of CD127 hepatitis B virus (HBV)-specific CD8⁺ T cells after successful antiviral treatment. Surface staining of HBV-specific CD8 T cells was performed using a HBV multimer [A. HBV Core 18-27 (FLPSDFFPSV), B. HBV Core 18-27 (FLPSDFFPSI)] and antibody to CD127, as described in the Materials and Methods. Data are shown as the percentage of multimer-positive CD8 T cells from 6 well responders (black bar) and 4 non responders (white bar) of CHB patients treated with telbivudine at 0 and 48 weeks respectively. (*P < 0.05).