Project/Area Number |
02454194
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Immunology
|
Research Institution | Jichi Medical School |
Principal Investigator |
MINATO Nagahiro Jichi Medical School, Dept. of Medicine, Associate Prof., 医学部, 助教授 (40137716)
|
Co-Investigator(Kenkyū-buntansha) |
HATTORI Masakazu Hokkaido Univ., Dept. of Veterinary Medicine, Assistant Prof., 獣医学部, 助手 (40211479)
|
Project Period (FY) |
1990 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥5,200,000 (Direct Cost: ¥5,200,000)
|
Keywords | Interleukin 2 / IL 2 receptor / Transgenic mice / CD45 / Phosphatidylinositol / Signal transduction / DNA-binding protein / リンフォカイン / 抗原レセプタ- / ハイブリド-マ / インタ-ロイキン3 / T細胞レセプタ- / アポプト-シス / フォスファチジルイノシト-ル結合蛋白 / 遺伝子再構成 / 細胞分化 |
Research Abstract |
By the analysis of human IL 2R(alpha)-transgenic mice, it was shown that the functional murine IL 24(beta)was expressed on normal resting T cells of limited subsets, including CD8^+ qlpha/beta, CD4^-8^- gamma/delta T cells and CD3^- NK cells, but not on the major CD4^+ alpha/beta T cells. Once these T cells are activated by IL 2, they exhibit several characteristic changes in the surface molecules. It was indicated that IL 2-activated T cells but not resting T cells, express high molecular weight Ly 5 isoform. This Ly 5 isofrom was shown to be derived from the full-length, unspliced MRNA as in the case of B cells, resulting in the change in the extracellular domain of-Ly 5 molecules. It was also shown that IL 2-activated T cells rapidly lose the expression of newly defined B7 surface antigen, which is normally expressed in the vast majority of resting T cells. Cloning and expression of B7. cDNA indicated that the B7 antigen was a new member of phosphatidylinositol(PI)-linked molecules. It was thus suggested that IL 2stimulation resulted in the -rapid activation of PI-PLC, which then cleaved. off the surface B7 molecules. Biological significance of the phenomenon remained to be seen. Finally, we have cloned a new gene(spa-1)which was specifically induced by the stimulation of T cells with either IL 2 or anti-TCR antibodies. Spa-1 encoded a 35 Kd protein with many kinase phosphrylation sites and probable DNA binding capacity. Since the expresssion of spa-1 gene showed general correlation with the proliferative status of T cells, it was implied that the product was somehow involved in the regulation of T cell proliferation by lymphokines and antigens.
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