| Project/Area Number |
11670294
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Osaka Universrty |
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Principal Investigator |
HIROI Takachika Research Institute for Microbial Diseases, Department of Mucosal Immunology, Osaka University Research Associate, 微生物病研究所, 助手 (80228824)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Nasal Immunization / IgA / B-1 cell / Vaccine / Mucosal Immunity / IL-15 / NALT / Th1 / Th2 / IL-5 / IL-5R / B-2細胞 / CMIS |
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| Research Abstract |
I show a new development results of the mechanisms of nasal vaccine system in this report supported by Grand-in-Aid for Scientific Research (C) (1999 - 2001) of Japan Society for the Promotion of Science as following.
1) Nasal Vaccine: Nasal vaccination with purified P. gingivalis fimbriae and cholera toxin (CT) is an effective immunization regimen for the induction of Ag-specific Thl and Th2 cell-derive IgA immune responses that possess the ability to inhibit bacterial attachment to epithelial cells. In addition, nasal recombinant BCG vector-based vaccine can secrete the V3 principal neutralizing epitope of HIV in serum, but not mucosal secreted IgA.
2) IgA producing mucosal B-l cell: IgA-committed (sIgA^+) B-l cells mainly resided in the lamina propria in the nasal cavity, while sIgA^+ B-2 cell formed in mucosal inductive site such as nasal associated lymphoid tissue. IL-5/IL-5R signaling pathway is important for the development of common mucosal immune system independent sIgA^+ B-l cell in nasal cavity in vivo. Further, IL-15 is also important cytokine for the differentiation of both sIgM^+, IgA- and slgM^-, sIgA^+ B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues. NALT is considered to be an important inductive site for the induction of antigen-specific mucosal and systemic immunity against nasally-administered vaccine antigen.
3) Organization of NALT: When LTα^<-/->, IL7-R^<-/-> and aly/aly mice were examined, known to lacking PLN and/or PP, NALT was observed in nasal cavity. Further, NALT like structure was also found in PP null mice generated by in vivo treatments with anti-IL7R mAb and LTβR-Ig. These findings suggested that NALT organogenesis is independently operated from a group of known lymphoid tissue generation cytokine signaling pathway.
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