| Project/Area Number |
05272105
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Juntendo University |
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Principal Investigator |
OKUMURA Ko School of Medicine, Juntendo University, Professor, 医学部, 教授 (50009700)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Takeshi Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (40028684)
NISHIMURA Yasuharu Kumamoto University Graduate School of Medicine Sciences, Professor, 大学院・医学研究科, 教授 (10156119)
YODOI Junji Institute for Virus Research, Kyoto University, Professor, ウィルス研究所, 教授 (80108993)
TAKATSU Kiyoshi The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (10107055)
SHIRAI Toshikazu School of Medicine, Juntendo University, Professor, 医学部, 教授 (30115860)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥199,600,000 (Direct Cost: ¥199,600,000)
Fiscal Year 1995: ¥64,600,000 (Direct Cost: ¥64,600,000)
Fiscal Year 1994: ¥63,000,000 (Direct Cost: ¥63,000,000)
Fiscal Year 1993: ¥72,000,000 (Direct Cost: ¥72,000,000)
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| Keywords | gene / signal transduction / autoantibody / B cell / MHC / transplantation / HIV / アポトーシス / FasL / IL-5リセプター / ADF / Lyn / SLE / 抗原ペプチド / TcR / DR / HSI / B70 / NZB / 移植拒絶 / IL-5 / I-E |
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| Research Abstract |
All members of this group are involved in the analysis of the relationships between immune dysfunction and disease on a genetic level. From antibodies and thymocytes to signal transduction mechanisms, this group study a wide range of subjects related to pathological causation. 1.) This group discovered the existence of linkage between an unusual MHC haplotype and the abnormal increase in B1 cells, which are important autoimmune antibody secreting B cells. They also reported that the novel gene, which was dubbed Imh-1, is closely linked to the TNF receptor family located on the end of the 4th chromosome. In addition, the group found that the Mott-1 gene, expressed in Mott cells, which are terminally differentiated from B1 lineage cells and present in patients with immune diseases and BCLL,is linked to the Imh-1 locus on the 4th chromosome. 2.) This group reported that B Cell specific bluton kinase (Brk) and JAK2 kinase can be activated via stimulation with IL5. The group also reported t
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hat irregularities in the IL-5R signal transduction pathway are responsible for the weak response of B cells to IL-5 stimulation in XID mice. 3.) This group was successful in cloning the gene which encodes CD86, a molecule which functions as a costimulatory molecule for T cell activation. By decreasing CD28/CD80 and CD86 signal expression, specific tolerance can be induced. In animal models of SLE,rheumatoid arthritis and atopic dermatitis which already show abnormal immune reactivity, they observed a significant suppression of the abnormal immune reactivity by decreasing CD28/CD80 and CD86 signal expression. 4.) In its continued investigation of the role of intracellular signaling in the activation of lymphocytes, this group, by developing Lyn kinase and HS1 deficient mice, analyzed the effects of dysregulation of these molecules on a molecular level. The group also determined the structure of tyrosine phosphory lated HS1 protein. 5.) This group showed that substitution of amino acids in sntigenic peptides altered the immune response to the antigenic peptides. 6.) This group demonstrated that HIV env protein gp 160 can bind to CaM,producing a dimmer that causes apoptosis due to intracellular accumulation of Ca2+. Furthermore, this group observed that binding of the env protein gp 120 to CD4 cells causes FasL production and an induction of apoptosis in CD4 and CD8 cells. Less
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