1993 Fiscal Year Final Research Report Summary
Function of Dendritic cells and their differentiation
| Project/Area Number |
03044086
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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, Faculty of Science, Kyoto University, 理学部, 助教授 (00115792)
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| Co-Investigator(Kenkyū-buntansha) |
ROMANI Nikolaus Associate Professor, Department of Science, Innsbruck University, 理学部, 准教授
GRANELLIーPIP アンジェラ ロックフェラー大学, 細胞生理免疫学部門, 准教授
STEINMAN Ralph M. Professor, Laboratory of Cellular Physiology and Immunology, The Rockefeller Uni, 細胞生理免疫学部門, 教授
GRANELLI-PIPERNO Angela Associate Professor, Laboratory of Cellular Physiology and Immunology, The Rocke
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| Project Period (FY) |
1991 – 1993
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| Keywords | Dendritic cells / Cell differentiation / Bone marrow cells / GM-CSF / T-cell activation / Precursors / Phagocytic activity |
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| Research Abstract |
Dendritic cells have been shown to originate from hematopoietic stem cells in the bone marrow. However, little is known about their differentiation. In the last year, we established a condition for inducing dendritic cell from proliferating precursors, and reported that GM-CSF induces the extensive growth of dendritic-cell precursors in suspension culture.
GM-CSF is known to induce the formation of mixed populations of granulocytes and macrophages in semi-solid colony systems. Therefore, we asked whether dendritic cells could arise from a colony-forming precursor that is common to phagocytes. Experiments to isolate cells from colonies that are induced by GM-CSF from MHC class II-negative precursors demonstrated that the colonies contain significant numbers of dendritic cells by several criteria, such as high levels of MHC class II expression, content of intracellular antigens, and antigen-presenting-cell function. Dendritic cells, therefore, represent a distinct immunostimulatory differentiation pathway that is induced by GM-CSF but share a common MHC class II-negative precursor with phagocytes.
Dendritic cells, while effective in sensitizing T cells to several different antigens, show little or no phagocytic activity. Since endocytosis is an important means whereby antigen are processed to form the peptides that are presented on MHC class II produces, it is not apparent how dendritic cells would present particle-derived peptides. We found that dendritic cells can internalize particular during an early stage in their development from proliferating progenitors. In addition, when the particles are Bacillus Calmette-Guerin (BCG) organisms, mycobacterial antigens are presented in a potent manner to T cells in vitro and in vivo.
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