| Project/Area Number |
11670441
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
MISAKI Yoshikata Univ of Tokyo, Hospital, Lecturer, 医学部・附属病院, 講師 (60219615)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Akihiro Univ of Tokyo, Hospital, Assistant Professor, 医学部・附属病院, 助手 (90261974)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Tolerance / anto antigen / antoimmune disease / OVA / anergy / dendritic cell / anto antibody / self / 卵白アルブミン / 自己免疫応答 / 自己抗原 / 免疫制御 / 末梢性免疫学的寛容 |
|---|
| Research Abstract |
It remains unknown why the T cell tolerance to nuclear autoantigens is impaired in systemic autoimmune diseases. To clarify this, we generated transgenic mice expressing OVA mainly in the nuclei (Ld-nOVA mice). When CD4^+ T cells from DO11.10 mice expressing a TCR specific for OVA_<323-339> were transferred into Ld-nOVA mice, they were rendered anergic but persisted in vivo for at least three months. These cells expressed CD44^<high>, CD45RB^<low> and were generated after multiple cell divisions, suggesting that anergy is not the result of insufficient proliferative stimuli. Whereas dendritic cells (DCs) from Ld-nOVA (TgDCs) efficiently induced proliferation of DO11.10 T cells, divided T cells stimulated by TgDCs in vivo exhibited a lower memory response than T cells stimulated by peptide-pulsed DCs. Furthermore, repeated transfer of TgDCs induced hyporesponsiveness of DO11.10 T cells in antigen-free wild-type recipients, suggesting that the repeated encounters with TgDCs rendered DO11.10 T cells persistent anergy. Since the state of TgDCs and peptide-pulsed DCs was almost the same except for the expression level of the agonistic ligand, the property of nuclear autoantigens which controls the tolerance of CD4^+ T cells might be the low and continuous expression of a self-peptide on DCs.
|
