| Project/Area Number |
09671940
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | Osaka Dental University |
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Principal Investigator |
UMEHARA Hisanori OSAKA DENTAL UNIVERSITY,LECTURE, 歯学部, 講師 (70247881)
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| Co-Investigator(Kenkyū-buntansha) |
DOMAE Naochika OSAKA DENTAL UNIVERSITY,PROFESSOR, 歯学部, 教授 (60115889)
NAGANO Yutaka OSAKA DENTAL UNIVERSITY,LECTURE, 歯学部, 講師 (80228048)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | NK cells / CD2 / signal pathway / cytotoxicity / tyrosine kinase / adapter proteins / PI3-kinase / PI 3キナーゼ |
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| Research Abstract |
To investigate signaling mechanisms of effector cell activation is important for improvement of adoptive immunotherapy for cancer patients. We investigated the functional roles of accessory molecule, CD2 and LFA-1 on NK and T cell activation. 1. Involvement of protein tyrosine kinase p72^<syk> (Syk) and phosphatidylinositol 3-kinase in CD2-mediated granular exocytosis in the natural killer cell line. (1) Crosslinking of CD2 induces granular exocytosis in tyrosine kinase and PI -3 kinase dependent fashion. (2) Crosslinking of CD2 induces tyrosine phosphorylation of Syk and activates its kinase activity. (3) Crosslinking of CD2 induces tyrosine phosphorylation of adapter protein, She and enhances PI 3-kinase activity associated with tyrosine phosphorylated adapter proteins, These results provide insight into the signaling pathways by which triggering of CD2 and CD16 on NK cells leads to cytolysis of target cells (J.Immunol. 159 : 1200, 1997). 2. Costimulation of T cells with CD2 augments TCRCD3-mediated activation of protein-tyrosine kinase p72^<syk>, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl. (1) Costimulation of CD2 with CD3 enhances tyrosine phosphorylation of Syk and its kinase activity. (2) Costiinulation of CD2 with CD3 enhances tyrosine phosphorylation of adapter proteins, Shc and Cbl. (3) Costimulation of CD2 with CD3 enhances IL-2 production and markedly augments T cell proliferation. These results indicate that CD2 is an activating receptor in NK cells and a major costimulatory molecules for T cells. These results indicate that CD2 is an important co- stimulatory receptor for CD3-mediated T cell activation and functions in concert with CD3(Int. Immunol. 10 : 833, 1998).
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