| Project/Area Number |
08457106
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
FUJIWARA Hiromi Osaka University Medical School, Associate Professor, 医学部, 助教授 (70116094)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1997: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1996: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | interleukin-12 / T cell / T cell actiration / interleukin-12 receptor / signal transduction / interferon-gamma / T細胞増殖 / インターロイキン12 / 抗原提示細胞 / CD40 / CD40 ligand / T-APC相互作用 |
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| Research Abstract |
Through our 2-year investigations, the following were revealed :
(1) Mechanisms underlying IL-12 production : IL-12 production is mediated by antigen-presenting cells/macrophages through stimulation with either CD40 ligand expressed on activated T cells or lipopolysaccharide (LPS). We have demonstrated that IL-12 production via these two pathways is regulated by cellular and soluble components involved in humoral immunity ; B cells and Th2 type cytokines (IL-10, IL-6 and IL-4).
(2) Establishment of an IL-12-responsive T cell clone (2D6) : We succeeded in establishing a T cell clone which can respond to a small amount of rIL-12 and be maintained in vitro cultures with rIL-12 alone. Establishing this clone permitted us not only to prepare a high-sensitive bioassay system capable of quantitating the amounts of IL-12 but also to investigate the following study.
(3) Signaling through IL-12-receptor (IL-12R). Stimulation of T cells with IL-12 rsults in the phosphorylation of two Janus kinases (TYK2 and JAK2) and two STAT proteins (STAT4 and STAT3). 2D6 cells could be maintained with either IL-12 or IL-2 (designated 2D6^<IL-12>, or 2D6^<IL-2> respectively). We found that stimulation of 2D6 with IL-12 activates STAT5 in addition to the above signaling molecules. Using these two 2D6 sublines, we observed that IL-12 stimulation induces proliferation in both sublines, but IFN-gamma production only in 2D6^<IL-12>. Our study also showed that TYK2 and STAT4/STAT3 are required for IL-12R signaling to IFN-gamma production whereas JAK2 and STAT5 are responsible for including the proliferation of 2D6 cells.
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