Project/Area Number |
04404035
|
Research Category |
Grant-in-Aid for General Scientific Research (A)
|
Allocation Type | Single-year Grants |
Research Field |
Immunology
|
Research Institution | Juntendo University |
Principal Investigator |
OKUMURA Ko Juntendo Univ. Sch. of Med.Prof., 医学部, 教授 (50009700)
|
Co-Investigator(Kenkyū-buntansha) |
AZUMA Miyuki Juntendo Univ. Sch. of Med.Assistant Prof., 医学部, 助手 (90255654)
KATO Kazunori Juntendo Univ. Sch. of Med.Assistant Prof., 医学部, 助手 (60233780)
RA Chisei Juntendo Univ. Sch. of Med.Associate Prof., 医学部, 講師 (60230851)
YAGITA Hideo Juntendo Univ. Sch. of Med.Associate Prof., 医学部, 助教授 (30182306)
屋部 登志雄 順天堂大学, 医学部, 助手 (50239836)
|
Project Period (FY) |
1992 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥7,000,000 (Direct Cost: ¥7,000,000)
|
Keywords | CD2 / CD48 / CD86 / CD80 / tolerance / allograft rejection / auto immune disease / monoclonal antibody / CD28 / 移植拒絶 / T cell / LAK / Thy-1 / ヘルパーT細胞 / VLA / 免疫寛容 / 拒絶反応 |
Research Abstract |
We performed the study to know how lymphocyte function associated antigens (LEA) on T cell are involved in various kind of immune responses. To analyzes it's mechanisms, we at first reported the effect of in vivo administration on the induction of tolerance by using mouse heart allograft experimental system. Then, it was revealed that absence of costimulatory signals from LFA-1 could induce T cell anergy. To investigate more detailed mechanisms of T cell tolerance, we further analyzed the role of other LFA in terms of T cell anergy induction. Then, we further analyzed the role of other LEA on T cell as well as those ligand molecules on antigen presenting all (APC). On the way of study, we could identify CD48 as unknown ligand of mouse CD2. By using monoclonal antibody to those molecules which we established, we could examine the biological significance of CD2 and CD48/LFA-3 pathway. Regarding to the signals from CD28 of T cell, we succeeded to identify unknown ligand on APC and name B70 (CD86). By using cDNA of B70 as well as monoclonal antibody, we could expand the study how CD28 and CD80/CD86 pathway is important to understand the intiation of T cell immune reponse as well as anergy induction and/or maintenance of T cell torelance. Especially using in vivo experimental systems, the administration of antiCD80 and antiCD86 could induce permanent torelance in the donor received allograft.
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