MASUMOTO Toshikazu Third Department of Internal Medicine School of Medicine, Ehime University, Associate Professor, 医学部・第三内科, 講師 (40243779)
AKBAR S. m. f. Third Department of Internal Medicine School of Medicine, Ehime University, Lecturer, 医学部・第三内科, 助手 (60190633)
|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
A role of antigen-presenting dendritic cells (DCs) is predicted during the persistent infection with hepatitis B virus (HBV). Using HBV-transgenic mouse (HBV-Tg), a mouse model of persistent HBV infection, we have shown that DCs from these HBV-Tg had defective function and altered phenotype. HBV-Tg were subjected to a regimen of vaccine therapy, and it was found that vaccine therapy resulted in reduced proliferation of HBV, negativity of hepatitris B surface antigen and e antigen. Moreover, vaccine therapy in HBV-Tg caused a recovery of DCs function almost to the levels of normal mouse. But, the cellular mechanism underlying the therapeutic role of vaccine therapy was not addressed.
Here, in order to clarify the underlying mechanism, the stimulatory capacity, surface markers and cytokine production by DCs from HBV-Tg before and after vaccine therapy were evaluated. Moreover, we attempted to see whether the functions of DCs have a prognostic importance during vaccine therapy.
Study on the mechanism of action of vaccine therapy revealed that in vaccine responders HBV-Tg, the improved functional capacity of DCs following vaccination was due to increased expression of surface antigens (MHC class II, CD86) and increased production of cytokines (IL-2, IL-12, and TNF-α).
The study on the prognostic importance of DCs during vaccine therapy showed that anti-KLH Ab titers in HBV-Tg represented a good marker of DC function. Next, we showed that only HBV-Tg with potent DC function responded to vaccine therapy ; whereas HBV-Tg with poor DC function did not respond. Thus, the function of DC prior to vaccine therapy appear to have a prognostic importance.
A single DNA vaccination in HBV-Tg resulted in therapeutic effect in some HBV-Tg. It is presumed that DNA vaccine may also cause the activation of DCs.
In summary, our data strongly indicate an important role of activation of DCs during vaccine therapy.