| Project/Area Number |
22390200
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
膠原病・アレルギー・感染症内科学
|
|---|
| Research Institution | Juntendo University (2012)
The University of Tokyo (2010-2011) |
|---|
Principal Investigator |
MORIMOTO Chikao 順天堂大学, 大学院・医学研究科, 客員教授 (30119028)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IWATA Satoshi 東京大学, 医科学研究所, 特任講師 (00396871)
HOSONO Osamu 東京大学, 医科学研究所, 講師 (50190210)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
YAMADA Taketo 慶應義塾大学, 医学部, 准教授 (60230463)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2010: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
|
|---|
| Keywords | CD26 / DPPIV 酵素 / CD28 / CD8T 細胞 / グランザイム B / xeno-GVHD / ヒト化 CD26 抗体 / IL-10 / CD26分子 / 共刺激 / 自己免疫疾患 / ヒト免疫系 / CD8T細胞 / GVHD / CD28分子 / サイトカイン産生 / グランザイムB / 細胞障害作用 / CD26/DPPIV / ヒト化CD26抗体 / Granzyme B / 糖尿病 / Fas Ligand |
|---|
| Research Abstract |
CD26 is a 110-KDa surface glycoprotein with DPPIV enzyme activity that has many biological functions. We showed that CD26 costimulation induced IL -10 production and CTLA-4 expression in CD4 T cells compared to CD28 costimulation suggesting that CD26 coslimulation has a negative activation pathway. We also showed that CD26 (high) CD8 T cells belong to the early effector memory T-cell subset and that CD26 mediated co-stimulation of CD8+T cells exerts a cytotoxic effect preferentially via gramzyme B, TNF-α and Fas-ligand compared to that obtained through CD28-mediated costimulation. Moreover, we showed that CD26+T cells play an important role in GVHD mediated by human lymphocytes, and that anti-CD26mAb is an effective treatment for GVHD in hu-PBL-NOG mouse model. In addition we found that genetical or pharmacological inhibition of CD26/DPPIV enhances endothelial growth both in vitro and in vivo, suggesting that DPPIV inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications. Our results strongly suggest that CD26/DPPIV is an appropriate therapeutic target for the treatment of selected immune disorders.
|
