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1993 Fiscal Year Final Research Report Summary

Analysis of the mechanism of negative and positive selection in the thymus : Use of CD4^+8^+ lymphoma cells as a model system

Research Project

Project/Area Number 04670294
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKeio University

Principal Investigator

TADAKUMA Takushi  Associate Professor Department of Microbiology, Keio University School of Medicine, 医学部, 助教授 (30051626)

Project Period (FY) 1992 – 1993
KeywordsFormation of T cell repertoire / Negative selection / Positive selection / CD4^+8^+ lymphoma / Apoptosis
Research Abstract

T cells are responsible for the discrimination of self and non-self. To acquire such activities, however, T cells must encounter two selections in the thymus, namely negative and positive selections. For analysis of the mechanism of these two selections, development of in vitro experimental systems is inevitable. We established CD4^+8^+ lymphomas transformed with radiation leukemia virus, and the following results were obtained.
(1)Lymphomas express either V beta 6 TcR or V beta 6/V beta TcR, and apoptosis is inducible in these cells when stimulated with anti-CD3 or anti-TcR antibodies, cortisone, Ca ionophores, cAMP, etc.
(2)The cells expressing V beta 8 TcR are susceptible to the inhibition of proliferation and apoptosis in the presence of Staphylococcus enterotoxin B(SEB) and antigen presenting cells (APC). The subsequent experiments revealed that B cells, dendritic cells and epithelial cells are effective as APC if they express class II antigens on the cell surface. Furthermore, I-E encoded class II antigens are found mainly used for antigen presentation, and anti-CD4 antibody could suppress the induction of apoptosis.
(3)The cells that escaped from cell death turned out to be CD4^+8^- cells. To accompany this change, various other changes were observed including the reduced expression of HSA antigens, the increased expression of H-2 antigens and the acquisition of the ability of IL-2L/IL-4 production when stimulated with phorbol ester plus Ca ionophore.
(4)Cyclosporin A could block both the induction of apoptosis and the acquisition of the ability of IL-2/IL-4 production, but did not influence the transition from CD4^+8^+ to CD4^+8^- phenotype. Various changes are induced by the signals via the same TcR, but our results suggest that different signal pathways may be used in these changes.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Yasutomi,D.: "Inhibition of programmed cell death by cyclosporin A;preferential blocking of cell death induced by signals via TCR/CD3 complet and its mode of action" Immunology. 77. 68-74 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 多田隈 卓史: "胸腺細胞で観察されるアポトーシスとT細胞レパートリーの形成" 病理と臨床. 10. 603-607 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohnishi,Y.: "Topoisomerase inhibitors induce apoptosis in thymocytes" Biochimica et Biophysica Acta. 1175. 147-154 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 多田隈 卓史: "リンパ球とアポトーシス" 蛋白質・核酸・酵素. 38. 109-115 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kizaki,H.: "Thymocyte apoptosis" Microbiol.Immunol.37. 917-925 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kizaki,H.: "Tumor necrosis factor-α enhances cAMP-induced programmed cell death in mouse thymocytes" Cytokine. 5. 342-347 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 多田隈 卓史: "bcl-2によるアポトーシス抑制と発癌" 医学のあゆみ. 165. 474 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 多田隈 卓史: "T細胞レパートリーの形成とアポトーシス" 実験医学. 11. 2287-2292 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 多田隈 卓史: "アポトーシス研究の現状" Biotherapy. 7. 1749-1756 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 多田隈 卓史(訳): "胸腺-T細胞の分化・成熟と自己・非自己識別能の獲得" 南江堂, 97 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasutomi, D.et al.: "Inhibition of programd cell death by cyclosporin A ; preferential blocking of cell death induced by signals via Tcr/CD3 complex and its mode of action." Immunology. 77. 68-74 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohnishi, Y.et al.: "Topoisomerase inhibitors induce apoptosis in thymocytes." Biochimica et Biophysica Acta. 1175. 147-154 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kizaki, H.et al.: "Thymocyte apoptosis" Microbiol.Immunol.37. 917-925 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kizaki, H.et al.: "Tumor necrosis factor-alpha enhances cAMP-induced programd cell death in mouse thymocytes." Cytokine. 5. 342-347 (1993)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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