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CD81 down-regulation on B cells is associated with the response to interferon-alpha-based treatment for chronic
Li-Ling Chang1, Pin-Nan Cheng, Jiann-Shiuh Chen
1Institute of Molecular Medicine, Medical College, National Cheng Kung University, Tainan 701, Taiwan, ROC.
Insights
Hepatitis C virus (HCV) treatment outcomes may be linked to CD81 molecule levels. Interferon-alpha therapy down-regulates CD81 expression, particularly in B-cells, indicating a host response associated with sustained virological response (SVR).
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- The CD81 molecule influences T-helper responses and may act as a hepatitis C virus (HCV) receptor.
- CD81's role in anti-HCV treatment efficacy requires further characterization.
- Interferon-alpha is a key therapeutic agent for HCV infection.
Purpose of the Study:
- To investigate interferon-alpha-induced alterations in lymphocytic CD81 expression.
- To compare CD81 levels and interferon-alpha responsiveness between healthy individuals, chronic HCV patients, and patients with sustained virological response (SVR).
Main Methods:
- Comparative analysis of surface CD81 levels in lymphocytes from different patient groups.
- In vitro treatment of lymphocytes and Daudi lymphoid cells with interferon-alpha, interferon-beta, and polyI:C.
- Investigation of the mechanism of CD81 suppression using 2-aminopurine.
Main Results:
- Healthy subjects and treatment-naïve HCV patients showed comparable baseline CD81 levels.
- In vitro interferon-alpha suppressed CD81 expression in lymphocytes from both groups.
- A significant down-regulation of B-cell CD81 was observed only in patients who achieved SVR.
- Interferons directly decreased CD81 expression in Daudi cells.
- The interferon-alpha effect on CD81 was partially restored by 2-aminopurine, implicating double-stranded RNA-activated kinase.
Conclusions:
- CD81 down-regulation is a host response to interferon-alpha therapy.
- CD81 modulation is an immunophenotype associated with successful anti-HCV treatment (SVR).
- Interferon-based therapies may directly impact CD81 expression levels.
Abstract:
The lymphocytic CD81 molecule, capable of modulating type-1/-2 T-helper responses and serving as a putative receptor for hepatitis C virus (HCV), might influence the outcome of anti-HCV treatment. This study characterized the interferon-alpha-induced alteration of lymphocytic CD81. The CD81 levels in healthy subjects and naïve chronic HCV patients were compared, with the results showing that the two groups had comparable surface CD81 levels for total peripheral blood lymphocytes, subpopulation-B, -T, and -NK cells. In vitro interferon-alpha treatment could suppress the CD81 expression from both groups. Subsequently, we compared the in vitro interferon-alpha modulatory effects on lymphocytic CD81 from patients having received anti-HCV therapy with either sustained virological response (SVR) or without SVR. There was a significant down-regulation of the B-cell's CD81 only in the SVR group. The CD81 modulation was further investigated using Daudi lymphoid cell line, showing declined surface CD81 levels following treatment with interferon-alpha, interferon-beta or polyI:C. Thus, interferons could directly decrease CD81 expression. The interferon-alpha effect could be restored by 2-aminopurine, suggesting that double-stranded RNA activated kinase might be involved in the suppression of CD81. In conclusion, CD81 down-regulation is a primary host response to interferon-alpha-based therapy and an immunophenotype associated with anti-HCV SVR.
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