1995 Fiscal Year Final Research Report Summary
Clarification of the role of cells constructing the thymic microenvironment in the early T cell development
| 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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| Keywords | T cell / Thymus / Stem cell / T cell progenitor / Adhesion molecule / Transcription factor / Stromal cell / Organ culture |
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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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Research Products
(11 results)
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[Publications] Hosono, M., Toichi, E., Hosokawa, M., Imamura, S., Gyotoku, J., Katsura, Y., Hosokawa, M.: "Development of autoreactivity and changes of T cell repertoire in different strains of aging mice." Mech Ageing Dev.78. 197-214 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Honda, M., Matsuo, K., Nakasone, T., Okamoto, Y., Yoshizaki, H., Kitamura, K., Sugiura, W., Watanabe, K., Fukushima, Y., Haga, S., Katsura, Y., Tasaka, H., Komuro, K., Yamada, T., Asano, T., Yamazaki, A., Yamazaki, S.: "Protective imune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette -Guerin vector candidate vaccine for human immuno-deficiency virus type 1 in small animals." Proc.Natl.Acad.Sci.USA. 92. 10693-10697 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Mazda, O., Aiba, Y., Hattori, N., Li, M., Fujimoto, S., Davis, M.M.Katsura, Y.: "Abrogation of the allelic exclusion in a T cell receptor beta chain gene transgenic mouse strain." Immunol.IInvest.24(6). 927-946 (1995)
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「研究成果報告書概要(欧文)」より
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