| Project/Area Number |
06044124
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kyoto University |
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Principal Investigator |
INABA Kayo Associate Professor, Graduate School of Science, Kyoto University, 大学院・理学研究科, 助教授 (00115792)
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| Co-Investigator(Kenkyū-buntansha) |
WITMERーPACK マージット デ ロックフェラー大学, 細胞生理免疫学部門, 上級研究員
STEINMAN Ralph m. Professor, Laboratory of Cellular Physiology and Immunology, The Rockefeller Uni, 細胞生理免疫学部門, 教授
WITMER-PACK Margit d. Senior Research Associate, Laboratory of Cellular Physiology and Immunology, The
WITMERーPACK マージット.デ ロックフェラー大学, 細胞生理免疫学部門, 上級研究員
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1995: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1994: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Dendritic cells / Antigen presentation / Cell differentiation, / Functional maturation / T cell activation / 単クローン抗体 |
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| Research Abstract |
Dendritic cells belong to the myeloid linearge of hematopoietic cells and are the most potent in T cell activation for in the initiation of immune responses. The aim of this project is futher clarification of the functional role of dendritic cells in vivo and in vitro in relation to the cellular development and maturation.
1) The NLDC-145 mAb recognizes a 205 kDa integral membrane protein which is expressed at high levels on murine dendritic cells and thymic epithelial cells (DEC-205). We reexamined cell specificity by mean of cytofluorographic and histological approaches and potential function of this molecule. DEC-205 can also be detected on many other subsets of leukocytes, particularly B cells. Although we have been unable to inhibit the alloreactivity that is induced by dendritic cells in vitro and in vivo, DEC-205 is shown to be rapidly internalized via coated pits and vesicles, and delivered to a multivesicular endosomal compartment resembling MIIC.A rabbit anti-DEC-205 IgG is pr
… More
esented by DCs to rabbit IgG-specific T cell hybridomas 100 times more efficiently than normal rabbit IgG.Considering that DEC-205 is a receptor with 10 C-type lectin domains, this molecule may be a novel endocytic receptor to capture glycoprotein antigens from extracellular space to specialized antigen processing compartment.
2) Age-related immunological dysfunction is demonstrated to be ascribable to the decreased T-cell stimulating activity of dendritic cells and B cells in SAMP1 mice. This change is primarily due to the reduced expression of class II and CD54, but not CD80 and CD86.
3) The HIV-1 promoter has two key transcriptional controls : NF-kB sites and Sp1 sites. Therefore, we looked for NF-kB and Sp1 factors in different cell types from human and mouse, using many biochemical and electromobility shift assays. Dendritic cells expressed high levels of all known NF-kB,but Sp1 was lacking. Quiescent T cells lacked active NF-kB but expressed Spl.By inducing heterologous dendritic-T cell syncytia, HIV brought together high levels of the essential factors for the viral promoter. This phenomenon would lead to chronic replication of HIV-1 without ostensible immune stimulation. Less
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