CD81 down-regulation on B cells is associated with the response to interferon-alpha-based treatment for chronic hepatitis C virus infection.
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.
Chang
Li-Ling
LL
Institute of Molecular Medicine, Medical College, National Cheng Kung University, Tainan 701, Taiwan, ROC.
Cheng
Pin-Nan
PN
Chen
Jiann-Shiuh
JS
Young
Kung-Chia
KC
D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060225:Tetraspanin 28
D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; D016898:Interferon-alpha; D060225:Tetraspanin 28