| Project/Area Number |
06454220
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KATSURA Yoshimoto Chest Disease Research Institute, Kyoto University, Professor, 胸部疾患研究所, 教授 (90027095)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Shinji Chest Disease Research Institute, Kyoto University, Assistant Professor, 胸部疾患研究所, 助手 (60199370)
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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 |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | T cell / Thymus / Stem cell / T cell progenitor / Adhesion molecule / Transcription factor / Stromal cell / Organ culture / 分化 / モノクローナル抗体 / 細胞間相互作用 |
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| Research Abstract |
We first investigated the role of adhesion molecules in T cell development. Various monoclonal antibodies (mAb) was added into the murine fetal thymus (FT) organ cultures, where T cell development from FT or fetal liver (FL) progenitors was induced by coculturing these cells with a deoxyguanosine-treated FT lobe. We found that anti-Pgp-1, anti-LFA-1 and anti-VLA-4 mAb severely inhibited the early phase of T cell development from FL but not FT.progenitors. These findings strongly suggest that interactions with elements in the thymic microenvironment through Pgp-1, LFA-1, and VLA-4 are indispensable for prethymic progenitors to develop into T cells.
We next investigated the role of transcription factors in the early thymic T cell development. We found that the synthesis of TCF-1 and GATA-3 proteins begins simultaneously in a fraction of the most immature population of FT cells, which have the phenotype of CD4^-CD8^-CD44^+CD25^-. It is also found that the T cell development from FL but FT progenitors in the FT organ culture system is severely inhibited by the addition of antisense oligonucleotides for either TCF-1 or GATA-3. These results strongly suggest that TCF-1 and GATA-3 play an essential role in the initiation of the earliest steps of T cell development in the thymus.
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