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.

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