Analysis of the mechanism for regulation of interleukin 2 gene expression
| Project/Area Number |
61570241
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
ONOUE Kaoru (1987) INSTITUTE FOR MEDICAL IMMUNOLOGY, KUMAMOTO UNIV. MEDICAL SCHOOL, 医学部, 教授 (60037497)
山本 雄正 熊本大学, 医学部, 助教授 (10158313)
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| Co-Investigator(Kenkyū-buntansha) |
尾上 薫 熊本大学, 医学部, 教授 (60037497)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Interleukin 2 mRNA induction / T cell activation / Interleukin 6 Accessory cell function / Protein Kinase C / アクセサリー細胞の役割 / プロテインキナーゼC / サイクロスポリンA / 白血病細胞のオートクリン増殖 / インターロイキン2 / Tリンパ球活性化 / カルシウム動員 / カルモジュリン / フォルボルエステル |
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| Research Abstract |
Interleukin 2 is a lymphokine essential for the growth and differentiation of lymphocytes. It is particularly important to note that helper T cells can be triggered by antigenic stimulation to express IL 2 and IL 2 receptor genes allowing them to grow by autocrine mechanism. A continued autocrine growth under some circumstances like a retroviral infection is supposed to be related to leukemic transformation of the cells. In this research project we analysed the triggering and regulatory mechanism of the IL 2 and IL 2 receptor expression using human T cells. 1) Studis of the roles of accessory cells (macrophages) required for triggering the peripheral blood T cells by anti-T3 monoclonal antibody revealed that the roles can be dissected into three : First, they present anti-T3 antibodies bound on the Fc receptors to T cells so that multiple interaction between anti-T3 molecules and T cell antigen receptor Ti/T3 molecules may result in the crosslinking of the receptors. Second, a certain
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molecules on macrophage cell surface appears to be required to interact with T cell surface. Our study revealed that the necessary molocules can be induced on U937 cells by recombinant interferon <gamma> (rIFN-<gamma>). Third, soluble factors released from macropages are essential for T cell triggering. Although the molecular nature of the factors are not yet determined, the combination of IL 1 and IL 6 were shown to replace macrophage factors. It was clarified that the IL 2 mRNA production can be induced only when the accessory cells fulfill the above three requirements. 2) Activation of protein kinase C was shown to play a critical role in regulating the magnitute of IL 2 gene expression. Thus a close correlation between the dose responses of protein kinase C activation and IL 2 mRNA production was observed. 3) In stimulated T cells, the IL 2 mRNA produced persists longer in cytoplasm than in the unstimulated T cells. 4) Cyclosporin A inhibits the induction of IL 2 mRN@a production without affecting Ca_<2+> mobilization and protein C kinase activation. 5) Two cases of adult T cell leukemia (ATL) patients were found whose leukemic cells produced IL 2 mRNA and IL 2 without any stimulation in culture and showing an autocrine growth in response to IL 2 produced by themselves, suggesting that the autocrine mechanism may be an inportant process in leukemogensis. Less
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Report
(2 results)
Research Products
(17 results)
