Project/Area Number |
11660304
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Basic veterinary science/Basic zootechnical science
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Research Institution | RIKEN (The institute of physical and chemical research) |
Principal Investigator |
IKE Fumio RIKEN (The institute of physical and chemical research), Division of Experimental Animal Research, Senior Researcher, 実験動物室, 先任研究員 (40183157)
|
Co-Investigator(Kenkyū-buntansha) |
HIRAIWA Noriko RIKEN (The institute of physical and chemical research), Division of Experimental Animal Research, Senior Researcher, 実験動物室, 先任技師(研究職) (30200380)
YOSHIKI Atsushi RIKEN (The institute of physical and chemical research), Division of Experimental Animal Research, Senior Researcher, 実験動物室, 先任研究員 (40212310)
KUSAKABE Moriaki RIKEN (The institute of physical and chemical research), Division of Experimental Animal Research (60153277)
日下部 守昭 理化学研究所, 遺伝子基盤研究部, 部長(研究職)
塚田 晃代 理化学研究所, 実験動物開発室, 研究員
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | thymus / tenascin-C / mouse / early development / T cell receptor beta chain / repertoire formation / CD25 / CD44 / プロT細胞 |
Research Abstract |
Tenascin-C (TN-C), one of the biggest extracellular matrix proteins, is expressed at considerable levels in the thymuses and spleens of adult mice. In order to investigate the function of TN-C in the immune system, we subjected TN-C deficient C3H/HeN congenic mice to sublethal X-irradiation. In the first week after irradiation, we found lineage negative-CD44 dull positive-CD25 positive thymocytes of TN-C deficient mice disappeared one day earlier than those of wild type mice. This strongly suggests that TN-C suppresses the differentiation of X-ray low sensitive thymic T cells which are believed as the major source of thymus reconstitution. We analyzed thymuses of wild-type mice biochemically and immunohistochemically. The expression of TN-C elevated strongly within a week after irradiation, and its expression was observed primarily at intra medullary lymphocytes and cortical blood vessels. On the functional assay using mixed lymphocyte reaction (MLR) method, responder cells from TN-C deficient GRS/A showed significantly low response to the stimulator cells from wild-type BALB/c than those from TN-C deficient BALB/c. This finding brought us the two possibilities ; one is that TN-C suppressed MLR overall via some suppressive factors or signals, and another is that TN-C worked to decrease the development of MLR reactive specific T cell clones. In order to clarify the latter possibility, we analyzed the T cell receptor β chain (Vβ) expression of peripheral lymph node T cells from TN-C deficient and wild-type GRS/A mice. However, we could not find any difference between them. On the contrary, FACS analyses of memory/activated T cells from non-stimulated spleens and lymph nodes indicated that the existence of TN-C might modify the induction of peripheral memory T cells.
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