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The Characteristics of Natural Killer Cells and T Cells Vary With the Natural History of Chronic Hepatitis B in Children.

ABSTRACT: Background and Aims: The immune status of children with chronic hepatitis B (CHB) in different phases is still unclear. The aim of this study was to investigate the phenotype and cytokine-producing ability of natural killer (NK) and T cells and to better understand the immune characteristics of children with different phases of CHB. Methods: Treatment-naive children with CHB were divided into groups with different clinical phases of CHB. Fresh peripheral blood drawn from hepatitis B virus (HBV)-infected and healthy children was processed to perform flow cytometric analysis. Results: A total of 112 treatment-naive children with CHB and 16 comparable healthy controls were included in this study. The expression of HLA-DR on NK cells and CD38 on T cells were upregulated, especially in the IA phase, in children with CHB compared with healthy controls. The ability of circulating NK cells instead of CD8+ T cells to produce IFN-γ in children with CHB was slightly increased, but TNF-α production seemed to be decreased compared with that in healthy controls. The expression of some activation markers varied among children with different phases of CHB, especially the higher CD38 expression found on T cells in the IA phase. Regression analysis revealed that IFN-γ and TNF-α production by NK cells and CD8+ T cells seemed to have positive correlations with ALT elevation and an activated status of NK cells or T cells. Conclusion: NK cells and T cells tended to be phenotypically activated (especially in the IA phase) in children with CHB compared with healthy controls. However, their cytokine-producing function was not obviously elevated, especially IFN-γ production by CD8+ T cells. More studies investigating the mechanism and observing the longitudinal changes in the immune status in children with CHB are needed.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC8656424 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators.MethodsThe CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry.ResultsIn the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011).ConclusionDuring the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group.

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The Characteristics of Natural Killer Cells and T Cells Vary With the Natural History of Chronic Hepatitis B in Children.

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