2006 Fiscal Year Final Research Report Summary
Characteristics features of immune producing dendritic cells : cross talk between dendritic cells. and B cells
Project/Area Number |
17590652
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Ehime University |
Principal Investigator |
ONJI Morikazu Ehime University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10112260)
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Project Period (FY) |
2005 – 2006
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Keywords | Dendritic cells / Hepatitis B surface antigen / Antibody to HBsAg / BAFF / Antigen-pulsed DC / Humoral immunity |
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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Research Products
(12 results)