Journal of Biomedical Science

, Volume 10, Issue 1, pp 120–135 | Cite as

Activation of Th1 immunity is a common immune mechanism for the successful treatment of hepatitis B and C: Tetramer assay and therapeutic implications

  • Sun-Lung Tsai
  • I-Shyan Sheen
  • Rong-Nan Chien
  • Chia-Min Chu
  • Hsiu-Chu Huang
  • Yen-Ling Chuang
  • Tzong-Hsien Lee
  • Shuen-Kuei Liao
  • Chen-Lung Lin
  • George C. Kuo
  • Yun-Fan Liaw
Original Paper


Both chronic hepatitis B and C virus (HBV and HCV) infections respond ineffectively to current antiviral therapies. Recent studies have suggested that treatment outcomes may depend on the development of type 1 T helper (Th1) and Th2 cell responses. Specifically, activation of Th1 immunity may play a major role in successfully treating hepatitis B and C. This model was revisited herein by evaluating immune responses in 36 HBV and 40 HCV patients with or without treatment, in an attempt to find a common immune mechanism for successful treatment. The immune responses in all examined cases were studied by peripheral blood mononuclear cell (PBMC) proliferation and cytokine responses to viral antigens, cytotoxic T lymphocyte (CTL) responses, enzyme-linked immunospot (ELISPOT) assay, and tetramer staining of virus-specific CD8+ T cells. The overall results revealed that all responders among both HBV- and HCV-infected cases displayed significantly higher PBMC proliferation to viral antigens with a predominant Th1 cytokine profile. Furthermore, the Th1-dominant responses were associated with significant enhancement of CTL activities and were correlated with ELISPOT data, while non-responders responded more weakly. During therapy, the numbers of tetramer-staining, virus-specific CD8+ T cells showed greater increases in responders than in non-responders (p=0.001). The frequencies determined by the tetramer assay were approximately 200-fold higher than data estimated by limiting-dilution analysis. In conclusion, activation of Th1 immunity accompanied by enhancement of CTL activity during therapy is a common immune mechanism for successfully treating hepatitis B and C, and therefore may have important therapeutic implications.

Key Words

Antiviral therapy Hepatitis B virus Hepatitis C virus ELISPOT assay Tetramer assay Limiting dilution analysis 


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Copyright information

© National Science Council 2003

Authors and Affiliations

  • Sun-Lung Tsai
    • 1
  • I-Shyan Sheen
    • 2
  • Rong-Nan Chien
    • 2
  • Chia-Min Chu
    • 2
  • Hsiu-Chu Huang
    • 2
  • Yen-Ling Chuang
    • 2
  • Tzong-Hsien Lee
    • 2
  • Shuen-Kuei Liao
    • 3
  • Chen-Lung Lin
    • 4
  • George C. Kuo
    • 5
  • Yun-Fan Liaw
    • 2
  1. 1.Department of Medical ResearchChi-Mei Medical Center, TainanYung-Kang City, Tainan HsienTaiwan
  2. 2.Liver Research UnitChang Gung Memorial HospitalTaiwan
  3. 3.Graduate Institute of Clinical MedicineChang Gung University College of MedicineTaipeiTaiwan
  4. 4.Department of SurgeryHong Kong University Medical Center, Queen Mary HospitalHong KongTaiwan
  5. 5.Chiron CorporationEmeryvilleUSA

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