Project/Area Number |
21590986
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
|
Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
NAKAMURA Yutaro 浜松医科大学, 医学部・附属病院, 助教 (60436962)
|
Co-Investigator(Kenkyū-buntansha) |
SUDA Takafumi 浜松医科大学, 医学部, 助教 (30291397)
NAGATA Toshi 浜松医科大学, 医学部, 教授 (90275024)
|
Research Collaborator |
KONO Masato 浜松医科大学, 医学部, 大学院生
KATO Masato 浜松医科大学, 医学部, 大学院生
KALINSKI Pawel University of Pittsburgh, Department of Surgery
GIERMASZ Adam S University of California San Francisco, Department of Hematology/Oncology
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 免疫学 / 感染症 / 細胞ワクチン / 免疫 / 細胞・組織 / 細胞,組織 |
Research Abstract |
The development of effective vaccine strategies for intracellular bacteria, including tuberculosis, is one of the major frontiers of medical research. Our previous studies showed that dendritic cell(DC) vaccine is a promising approach for eliciting protective immunity against intracellular bacteria. Recently, we found that more preferable DCs were generated by the presence of IL-4 and IFN-γduring the maturation of mouse DCs(type-1 polarization), resulting in improved induction of anti-tumor immunity in cancer. Here we show that such type-1 polarized DCs promote dramatic enhancement of protective immunity against an intracellular bacterium, Listeria monocytogenes. Murine bone marrow-derived DCs were cultured and matured with LPS, IL-4 and IFN-γ(type-1 polarized DCs ; DC1), and with LPS alone(non-polarized DCs ; DC). DCs were loaded with listeriolysin O(LLO) 91-99, H2-K^d-restricted epitope of L. monocytogenes, and were injected into naive BALB/c mice intravenously. Type-1 polarized DCs vaccine strongly enhanced LLO 91-99-specific CD8^+T cells exhibiting epitope-specific cytotoxic activity and IFN-γproduction, leading to significant induction of protective immunity against L. monocytogenes. Type-1 polarized DCs are potential candidates for enhancing protective immunity in the design of effective vaccination strategies against intracellular bacteria.
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