| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
To explore the mechanism of induction of antigen-specific humoral immune response by antigen-pulsed dendritic cells, we cultured murine spleen DCs with hepatitis B surface antigen (HBsAg) to produce HBsAg-pulsed spleen DCs. HBsAg-pulsed spleen DCs were immunogenic in vitro because they produced increased amounts of proinflammatory cytokines compared to unpulsed spleen DCs. In addition, murine spleen DCs induced proliferation of HBsAg-specific memory lymphocytes. Administration of HBsAg-pulsed DC induced antibody to HBsAg (anti-HBs) and also HBsAg-specific T cells. In general, both anti-HBs and HBsAg-specific lymphocyte were detected in HBsAg-pulsed DC-injected mice, however, kinetic studies revealed that in some cases, anti-HBs were detected before presence of HBsAg-specific T cells. This indicates that antibody production by antigen-pulsed DCs may be mediate independent of T cell helping in some cases. However, this should be confirmed by further studies.
Next, translation research was done in human with HBsAg-pulsed human blood DCs. The culture conditions were optimized so that immunogenic HBsAg-pulsed human blood DCs can be prepared by culturing human blood DCs with HBsAg in commercial vaccine. Administration of HBsAg-pulsed DCs induced anti-HBs in normal volunteer as well as in non responder of hepatitis B vaccine; HBsAg-specific T cells were detected in the peripheral blood of HBsAg-pulsed DC injected individuals. Two important findings wer also found from this study, HBsAg-pulsed human blood DCs produced increased amounts of B cells activating factor of tunic necrosis factor family (BAFF) compared to that produced by unpulsed human blood DCs. In addition, administration c HBsAg-pulsed DCs induced high levels of BAFF in the sera of normal human volunteers. Taken together, it may be postulated that antibody production by antigen-pulsed DCs may independent be mediated without T cell help and this activation of BAFF may play a critical role in this regard
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