FRI-151
Characterization of regulatory T cells and the role of PD-1 and
TNF-alpha in spontaneous hepatitis B surface antigen
seroclearance in chronic hepatitis B
Fen Liu1, Saisai Zhang1, Fung Yu Huang1, DannyWong1, Lung-Yi Mak1,
Ka-Shing Cheung1, Ching Lung Lai1, Man-Fung Yuen1,Wai-Kay Seto2.
1The University of Hong Kong, Medicine, Hong Kong, Hong Kong; 2The
University of Hong Kong, Medicine, Hong Kong, Hong Kong
Email: [email protected]
Background and aims: Spontaneous seroclearance of hepatitis B
surface (HBsAg) is associated with enhanced HBV-specific T cell
response. CD4+CD25high CD127low/- regulatory T cells (Tregs) possess
HBV-specific immunoregulatory effects. Whether Tregs are involved
in HBsAg seroclearance remains to be determined. We aimed to
investigate the changes of Tregs in chronic hepatitis B (CHB) patients
achieving spontaneous HBsAg seroclearance.
Methods: We recruited CHB patients who achieved spontaneous
HBsAg seroclearance for at least 6 months (experimental group), and
treatment-naïve age- and sex-matched hepatitis B e antigen-negative
controls. Peripheral blood mononuclear cells (PBMCs) were isolated
using Ficoll-Pague density gradient centrifugation method. The
frequency, transcriptional factor (FoxP3), different inhibitory phenotypes
(PD-1, CTLA-4, LAG-3 and GITR), and immunoregulatory
cytokines (TNF-alpha, IFN-gamma, TGF-beta, IL-10 and IL-17A) of
Tregs were detected by multicolor flow cytometry (BD LSR Fortessa
Analyzer, San Jose, CA).
Results: Twenty-seven patients with HBsAg seroclearance were
recruited (mean age 53.70 ± 7.93 years, 55.6% male). Median duration
from achieving HBsAg seroclearance to PBMCs collection was 1.47(interquartile range 0.72–2.73) years. Median HBsAg and HBV DNA
levels in the control group (n = 27) were 2.74 (1.59-3.42) log IU/ml
and 3.22 (1.96-3.81) log IU/ml, respectively. The mean frequency of
Tregs and the expression of FoxP3 in the experimental group were
comparable to the control group (3.39% vs. 3.35% and 65.95% vs.
65.37%, respectively; both p > 0.05). The mean expression of PD-1 on
Tregs was significantly lower in the experimental group than that in
the control group (9.65% ± 3.27 vs. 12.03% ± 4.49; p = 0.03). No
significant differences were found for CTLA-4, LAG-3 and GITR
phenotypes (all p > 0.05). In the experimental group, Tregs had a
greater expression of TNF-alphawhen compared to the control group
(37.89% ± 9.50 vs. 28.87% ± 9.04; p = 0.001), with no significant
differences noted in the production of IFN-gamma, TGF-beta, IL-10
and IL-17A (all p > 0.05). In the control group, a significant inverse
correlation was observed between the proportion of TNF-alphaexpressing
Tregs and serum level of HBsAg (r = -0.669, p < 0.001).
Conclusion: The reduced expression of PD-1 and/or increased
production of TNF- alpha may attenuate the immunosuppressive
capability of Tregs, and may contribute to the “functional cure” of
CHB. 作者: StephenW 时间: 2019-4-17 18:36
