| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
We have previously reported that hepatitis B virus (HBV) transgenic mouse [TM] had a low responsiveness in regard to specific antibody production to a t-cell dependent antigen keyhole limpet hemocyanin (KLH) , due to significantly lower T-cell stimulatory capacity of transgenic dendritic cells (DRCs) , possibly as a result of significantly lower level of expression of Ia antigen on DRCs. Treatment of TM with mouse gamma-IFN resulted in an increased expression of MHC class II (Ia antigen) on spleen DRCs in vivo and in vitro. TM primed with an optimum dose of KLH couold not produce anti-KLH antibody in sera, but injecting them with KLH along with gamma-IFN enabled them to produce anti-KLH antibody. KLH-primed normal mice derived T/B cells could produce anti-KLH antibody, when cultured with DRCs form gamma-IFN treated TM expressing higher level of Ia antigen, but not with DRCs from unreated or PBS-treated TM.Therefore, these experiments have shown that the level of expression of Ia antige
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n on DRCs is a critical factor for its antigen presenting cell (APC) capability in immune response and its modulation by gamma-IFN can overcome the immune response defects in murine HBV-carriers by immunomodulatory effect and possibly by some antiviral activity.
Recently, it has been reported that human HBV-carriers can produce anti-HBs in vivo and the inability to detect anti-HBs in sera in HBV-carriers, reported so far has been a matter of technical limitation. When we injected high dose of HBV vaccine to TM in vivo, anti-HBs antibody was appeared in sera of TM.When the whole spleen cells of HBs antigen-primed TM were culture with whole cells, APC of DRCs from unprimed normal mice, the culture supernatant showed anti-HBs. The inability to mount an antibody response to HBs antigen in HBV-TM in not due to a tolerance resulted from the circulating HBs antigen in sera, but the defects in DRCs may be the primary factor for this.
In conclusion, there is a possibility that drugs modulating the APC capacity of DRCs are useful for treatment of HBV carriers. Less
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