| Summary: | 碩士 === 國立成功大學 === 分子醫學研究所 === 93 === Available evidence demonstrated that interferon-alpha (IFN-��) along with ribavirin exerted apparent therapeutic effect on clearance of hepatitis C virus. Beside virological factors, host factors, such as certain immunological regulators, seem to affect the outcome of antiviral treatment of IFN-�� and ribavirin since both agents have shown immunomodulation. Among these, human CD81, a HCV E2 binding protein, might participate in HCV escaping mechanism from host immune surveillance. Surface CD81 molecule accounts for the recognition of immune response which is broadly coordinated between many cell types, such as B, T, natural killer (NK) and other stromal cells. In this study, CD81 expression was assessed on the surface of fresh-isolated peripheral blood mononuclear cells (PBMC) from healthy donors and naïve HCV patients and the surface of IFN-��-cultivated PBMCs from healthy donors, naïve HCV patients, and responders and non-responders of combination therapy. Data showed that no difference of CD81 expression on T, B and NK cells existed between healthy subjects and patients with HCV infection. There was no difference of IFN-��-induced CD81 down-regulation between healthy donors and naïve patients. However, treatment of IFN-�� significantly decreased CD81 expression on B cells in PBMC from patients with sustained virological response, but not those without it. For the molecular mechanisms, we showed that IFN-���ntreatment reduced the surface CD81 protein, but not the CD81 RNA. The IFN-�� function could be restored by 2-aminopurine, suggesting double-stranded RNA activated kinase (PKR) were involved. The relevance of therapeutic responses with IFN-��-induced surface-protein modulation was also examined in a longitudinal study. CD81 expression on subpopulations of PBMCs was not significantly different between virological responders and non-responders. However, preliminary results from longitudinal investigation showed that the expression of HLA-ABC molecules was significantly up-regulated on B cells and monocytes from virological responders, but not from non-responders. In conclusion, our data suggested the modulation effect of IFN-�� on CD81 expression is not related to HCV infection. The alteration of expression of surface CD81 on B cells might be an indicator for the outcome of IFN-�� treatment. Results from longitudinal study might suggest that Th1 responses could be augmented during IFN-�� treatment in the virological responders in HCV infection.
|
|---|
