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Published on: October 20, 2021
Changes of costimulatory molecule CD28 on circulating CD8+ T cells correlate with disease pathogenesis of chronic
Xuefen Li1, Haishen Kong2, Li Tian3
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China ; Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
Insights
In chronic hepatitis B (CHB) patients, CD8+ T cells show altered CD28 expression, with a decrease in the CD8+CD28+/CD8+CD28- T cells ratio, indicating immune dysregulation and disease progression.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Costimulatory signals, particularly CD28, are essential for effective antiviral immunity.
- Chronic hepatitis B (CHB) infection is associated with impaired T cell function.
- Understanding T cell dynamics in CHB is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the expression of the costimulatory molecule CD28 on circulating CD8+ T cells in patients with CHB.
- To evaluate the ratio of CD8+CD28+ to CD8+CD28- T cells (CD8+CD28+/CD8+CD28- T cells ratio) in CHB patients.
- To assess the correlation of these T cell subpopulations and their ratio with disease activity, viral load, and treatment response.
Main Methods:
- Flow cytometry was used to quantify CD8+CD28+ and CD8+CD28- T cell subpopulations in 70 CHB patients and 56 healthy controls.
- A longitudinal study of 48 CHB patients over 52 weeks was conducted.
- The CD8+CD28+/CD8+CD28- T cells ratio was calculated and correlated with hepatitis B virus (HBV) loads, hepatitis B e antigen (HBeAg) status, and antiviral therapy outcomes.
Main Results:
- CHB patients exhibited higher proportions of CD8+CD28- T cells and a lower CD8+CD28+/CD8+CD28- T cells ratio compared to healthy controls.
- The CD8+CD28+/CD8+CD28- T cells ratio significantly correlated with HBV viral loads.
- HBeAg-positive individuals showed increased CD8+CD28- T cells and a decreased ratio. Efficient antiviral therapy led to a decrease in CD8+CD28- T cells and an increase in CD8+CD28+ T cells and the ratio.
Conclusions:
- Aberrant CD28 expression on circulating CD8+ T cells and altered CD8+CD28+/CD8+CD28- T cells ratio are indicative of T cell activation dysregulation in CHB.
- These immunological changes are linked to the pathogenesis of chronic HBV infection.
- Monitoring CD28 expression on CD8+ T cells may serve as a biomarker for disease status and treatment efficacy in CHB.
Abstract:
Costimulatory signals are critical for antiviral immunity. The aim of this study was to evaluate the change of costimulatory molecule CD28 on circulating CD8+ T cells in chronic hepatitis B patients (CHB). Seventy CHB patients and fifty-six healthy controls were included, and forty-eight CHB patients were recruited for 52 weeks of longitudinal investigation. The proportions of circulating CD8+CD28+ and CD8+CD28- subpopulations were determined by flow cytometry, and the CD8+CD28+/CD8+CD28- T cells ratio was calculated. Compared with the subpopulation in healthy controls, high proportions of CD8+CD28- subpopulation were observed in CHB patients. Similarly, the CD8+CD28+/CD8+CD28- T cells ratio was significantly decreased in CHB patients compared with healthy controls and correlated significantly with hepatitis B virus (HBV) loads. High proportions of CD8+CD28- subpopulation and low CD8+CD28+/CD8+CD28- T cells ratio were observed in hepatitis B e antigen- (HBeAg-) positive individuals as compared with that in HBeAg-negative subjects. A significant decrease in CD8+CD28- subpopulation, increase in CD8+CD28+ subpopulation, and CD8+CD28+/CD8+CD28- T cells ratio were seen in those patients who received efficient antiviral therapy. Thus, aberrant CD28 expression on circulating CD8+ T cells and the CD8+CD28+/CD8+CD28- T cells ratio reflect the dysregulation of T cell activation and are related to the pathogenesis of chronic HBV infection.
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