Intrahepatic CD8⁺ T-lymphocyte response is important for therapy-induced viral clearance in chronic hepatitis B infection

详细信息    查看全文

• 作者：Thjon J. Tang ; Jaap Kwekkeboom ; Shanta Mancham ; Rekha S. Binda ; Robert A. de Man ; Solko W. Schalm ; Johannes G. Kusters and Harry L.A. Janssen
• 刊名：Journal of Hepatology
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：43
• 期：1
• 页码：45-52
• 全文大小：290 K

文摘

Background/Aims

To determine which immune cells contribute to HBV-clearance during antiviral therapy, we performed a longitudinal analysis of intrahepatic immune cells during interferon-α therapy of chronic HBV-patients using the FNAB technique.

Methods

Twenty chronic HBeAg⁺-patients were treated with pegylated α-interferon combined with lamivudine or placebo for 52 weeks. FNAB and blood specimens were obtained at week 0, 2, 8 and 52. CD4⁺- and CD8⁺ T-lymphocytes, CD56⁺ cells, IFNγ and granzyme B (GrB) were immunocytochemically quantified.

Results

The relative numbers of CD56⁺ cells and CD8⁺ T-lymphocytes were significantly higher in FNAB compared to blood at all time-points. Responders (n=9) exhibited significant increases in intrahepatic CD8⁺ and CD8⁺GrB⁺ lymphocytes, a small elevation in CD8⁺IFNγ⁺ T-lymphocytes, no change in CD4⁺ T-lymphocytes, and a decrease in intrahepatic CD56⁺ cells during the first weeks of therapy. In non-responders (n=11) no significant changes in CD4⁺- and CD8⁺ T-lymphocytes and an increase in intrahepatic and CD56⁺ cells were observed during therapy.

Conclusions

The intrahepatic CD8⁺ T-lymphocyte, but not the CD4⁺ T-lymphocyte or NK/NKT-cell response, is important for HBV clearance during interferon-α therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms.