| Project/Area Number |
17590965
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
NAGAYAMA Yuji Nagasaki University, Graduate School of Biomedical Sciences, Department of Medical Gene Technology, Atomic Bomb Disease Institute, professor, 大学院医歯薬学総合研究科, 教授 (30274632)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAITOH Ohki Nagasaki University, Graduate School of Biomedical Sciences, Department of Medical Gene Technology, Atomic Bomb Disease Institute, research fellow, 大学院医歯薬学総合研究科, 助手 (60380961)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | thyroid autoimmunity / thyrotropin receptor / regulatory T cells / autoantibody / Graves' disease / adenovirus |
|---|
| Research Abstract |
1. Suppression of disease development by CD4^+CD25^+ regulatory T cells (Treg) : Depletion of Treg by anti-CD25 antibody induced Graves' hyperthyroidism in 30 % of resistant C57BL/6 mice, and increased serum T_4 levels by 200 % in susceptible BALB/c mice. This effect was attributed to decreased stimulatory antibody titers and increased blocking antibody titers. Furthermore, in transfer experiments to naive wt mice, splenocytes from Graves' mice induced little anti-TSHR antibody, but CD25-depleted splenocytes did low but significant levels of antibody.
2. Suppression of disease development by regulatory cytokines : adenovirus expressing IL-10 or TGF-beta (both are regulatory cytokines) were constructed, and administered to mice together with adenovirus coding the TSHR (Ad-TSHR). Only Ad-IL-10 significantly inhibited hyperthyroidism.
3. Suppression of disease development by apoptosis-inducing Fas ligand (FasL) : Adenovirus expressing FasL was constructed, and infected into dendritic cells (DCs) derived from bone-marrow cells by using GMCSF and IL-4 together with Ad-TSHR. These DCs inhibited anti-TSHR immune response and development of Graves' disease induced by intramuscular injection of Ad-TSHR.
4. TSHR-specific T cell lines are now being established by the TSHR protein and three : peptides which induced IFNgamma release in recall assay. Abilities of individual clones to produce cytokine(s) and to induce hyperthyroidism as well as amino acid sequences of T cell receptors will be studied.
|
