1997 Fiscal Year Final Research Report Summary
Microenvironment for thymocyte differentiation, selection and clonal elimination
| Project/Area Number |
07407066
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Tohoku University |
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Principal Investigator |
ITOH Tsunetoshi Tohoku Univ.School of Medicine Professor, 医学部, 教授 (90004746)
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| Co-Investigator(Kenkyū-buntansha) |
YAGI Hideki Tohoku Univ.School of Medicine Research Associate, 医学部, 助手 (40250740)
NAKAMURA Masanori Tohoku Univ.School of Medicine Associate Professor, 医学部, 助教授 (50180394)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Thymus / Thymocytes / Differentiation / Selection / Clonal deletion / Microenvironment / Apoptosis / Cell death |
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| Research Abstract |
We obtained following conclusions through the 3-years' project entitled "Microenvironment for thymocyte differentiation, selection and clonal elimination".
1. The pattern of cell deaths in the thymus and in the lymph nodes, where thymocytes are clonally deleted or affinity maturation takes place with B cells in germinal centers, respectively, was demonstrated not to be apoptosis. In the thymus and at germinal centers, thymocytes or B cells die by pyknosis. It is thus urgently necessary to reconsider what the apoptosis is and what the significance of clonal deletion if it is not accomplished by apoptosis in the thymus.
2. Severe and massive thymocyte death due to steroid administration has long been believed to be apoptosis. Careful morphological examination of in vivo thymus clearly revealed that even after steroid treatment, thymocytes died by pyknosis, and immediately after they died by pyknosis they were engulfed by cortical macrophages.
3.Plain electron microscopy on FACS-sorted thymocytes based on FLS (cell size) and surface markers identified five morphologically distinct subpopulations possibly at different differentiation stages. This analysis would be extremely useful for future in situ examination of thymocytes for pursuing their differentiation pathway within the thymus.
4. Immunological tolerance was successfully established by injecting BALB/c thymic epithelial cell line (IT-76MHC) into allogeneic mouse thymuses (C3H). Mechanisms remain to be elucidated.
5. Two different macrophage subsets were recognized in mouse thymus in terms of their location, surface phenotypes, morphology and functions. This finding would consequently lead to more precise investigation of the thymic microenvironment.
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[Publications] Pieters, R.H., Albers, R., Bleumink, R., Snoeij, N.J., Itoh, T., Seinen, W., and Penninks, A.H: "The thymus atrophy-inducing organotin compound DBTC inhibits the binding of thymcytes to thymic epithelial cells." Int.J.Immunopharmac.17. 329-337 (1995)
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[Publications] Nakamura, M., Yagi, H., Kayaba, S., Ishii, T., Gotoh, T., Itoh, T.: "Most thymocytes die in the absence of DNA fregmentation." Arch.Histol.Cytol.58. 249-256 (1995)
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[Publications] Nanno, M., Hata, M., Shimada, S., Doi, H., Satomi, S., Yagi, H., Nakamura, M., Sakata, T., Suzuki, R., and Itoh, T.: "Induction of TCRgammadelta^+ cells from thymocytes stimulated by a fetal liver-derived hepatocyte clone." J.Immunol.155. 2918-2927 (1995)
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[Publications] Nakamura, M., Yagi, H., Kayaba, S., Ishii, T., Gotoh, S., Ohtsu, S., and Itoh, T.: "Death of germinal center Bcells without DNA fragmentation." Eur.J.Immunol.26. 1211-1216 (1996)
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[Publications] Yagi, H., Matsumoto, M., Nakamura, M., Makino, S., Suzuki, R., Harada, M., and Itoh, T.: "Defect of thymocyte emigration in a T-cell deficiency strain (CTS) of mouse." J.Immunol.157. 3412-3419 (1996)
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[Publications] Nakamura, M., Yagi, H., Ishii, T., Kayaba, S., Soga, H., Gotoh, T., Ohtsu, S., Ogata, M., and Itoh, T.: "DNA fragmentation is not the primary event in glucocorticoid-induced thymocyte death in vivo." Eur.J.Immunol.27. 999-1004 (1997)
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[Publications] Soga, H., Nakamura, M., Yagi, H., Kayaba, S., Ishii, T., Gotoh, T., Itoh, T.: "Heterogeneity of thymic macrophages. I.Immunohistochemical analysis." Arch.Histol.Cytol.60. 53-63 (1997)
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[Publications] Ishii, T., Nakamura, M., Yagi, H., Soga, H., Kayaba, S., Gotoh, T., Satomi, S., and Itoh, T.: "Glucocorticoid-induced thymocyte death in murine thymus : The effect at later stages." Arch.Histol.Cytol.60. 65-78 (1997)
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[Publications] Koja, S., Doi, H., Satomi, S., Fujimori, K., Takemura, M., Ohkohchi, N., Miura, S., Takeda, Y., Morimoto, K., Itoh, T., Taguchi, Y., and Okazaki, H.: "Induction of tolerance to islet and skin allografts by intrathymic inoculation of thymic stromal cell clones in mice." Transplantation Proc.29. 765-766 (1997)
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