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Microenvironment for thymocyte differentiation, selection and clonal elimination

Research Project

Project/Area Number 07407066
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionTohoku University

Principal Investigator

ITOH Tsunetoshi  Tohoku Univ.School of Medicine Professor, 医学部, 教授 (90004746)

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)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsThymus / Thymocytes / Differentiation / Selection / Clonal deletion / Microenvironment / Apoptosis / Cell death
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.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Nakamura, M., et al.: "Most thymocytes die in the absence of DNA fragmentation." Arch.Histol.Cytol.58. 249-256 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakamura, M., et al.: "Death of germinal center Bcells without DNA fragmentation." Eur.J.Immunol.26. 1211-1216 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yagi, H., et al.: "Defect of thymocyte emigration in a T-cell deficiency strain(CTS)of mouse." J.Immunol.157. 3412-3419 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakamura, M., et al.: "DNA fragmentation is not the primary event in glucocorticoid-induced thymocyte death in vivo." Eur.J.Immunol.27. 999-1004 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Soga, H., et al.: "Heterogeneity of thymic macrophages.I. Immunohistochemical analysis" Arch.Histol.Cytol.60. 53-63 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yagi, H., et al.: "Ultrastural analysis of mouse thymocyte subpopulations" Eur.J.Immunol.27. 2680-2687 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Moriguchi, S., and Itoh, T.: "Vitamin E enhances T cell differentiation through increased epithelial cell function in rat thymus." Nutrition Res.17. 873-883 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yagi, H., Nakamura, M., Ishii, T., Kasahara, S., and Itoh, T.: "Ultrastructural analysis of mouse thymocyte subpopulations." Eur.J.Immunol.27. 2680-2687 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] He, W., Sakabe, K., Okuma, M., Itoh, T., and Seiki, K.: "Sex steroid modulation of signal transduction in thymus epithelial cell culture." Pathophysiology.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yagi, H, et al.: "Defect of thymocyte emigration in a T-cell deficiency strain(CTS)of mouse." J.Immunol.157. 3412-3419 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura, M., et al.: "DNA fragmentation is not the primaryevent in glucocorticoid-induced thymocyte death in vivo" Eur.J.Immunol. 27. 999-1004 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Soga, H., et al.: "Heterogeneity of thymic macrophages. I.Immunohistochemical analysis." Arch.Histol.Cytol.60. 53-63 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishii, T., et al.: "Glucocorticoid-induced thymocyte death in murine thymus" Arch.Histol.Cytol. 60. 65-78 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koja, S., et al.: "Induction of tolerance to islet and skin allografts by intrathymic inoculation of thymic stromal cell clones in mice." Transplantation Proc.29. 765-766 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yagi, H., et al.: "Ultrastructural analysis of mouse thymocyte subpopulations." Eur.J.Immunol.27. 2680-2687 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura, M., et al.: "Deaths of germinal center B cells without DNA fragmentation." Eur. J. Immunol.26. 1211-1216 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yagi, H., et al.: "Defect of thymocyte emigration in a T-cell deficiency strain (CTS) of mouse." J. Immunol.157. 3412-3419 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura, M., et al.: "DNA fragmentation is not the primary event in glucocorticoid-induced thymocyte death in vivo." Eur. J. Immunol.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Soga, H., et al.: "Heterogeneity of thymic macrophages. I. Immunohistochemical analysis." Arch. Histol. Cytol.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishii, T., et al.: "Glucocorticoid-induced thymocyte death in murine thymus." Arch. Histol. Cytol.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura,M.: "Most thymocyte die in the Absence of DNA fragmentation" Arch.Histol.Cytol.58. (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yagi,H.: "A defect of thymocyte emigration in a T-cell deficiency strain(CTS) of mouse" J.Immunol.(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakamura,M.: "Deaths of germinal center β cells without DNA fragmentaion" Eur.J.Immunol.(印刷中). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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