The abnormality of self-recogition by T cells in autoimmune state
| Project/Area Number |
61570313
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Shimane Medical University |
|---|
Principal Investigator |
KOTANI Hiroyuki 3rd Division of Internal Medicine, Shimane Medical University, 医学部, 助手 (90135905)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKANE Tsuyoshi 3rd Division of Internal Medicine, Shimane Medical University, 医学部, 助教授 (40127519)
|
|---|
| Project Period (FY) |
1986 – 1987
|
| Project Status |
Completed (Fiscal Year 1987)
|
| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1987: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Keywords | Autoreactive T cell clone / Dual immunoregulatory function / MHC class II antigen / 自己免疫疾患 / 自己リンパ球混合培養反応 / 自己認識機構 / HLAクラス【II】抗原 / ヘルパー機能 / サプレッサー機能 / T3関連抗原 / グリコシレーション |
|---|
| Research Abstract |
It is well-verified that human immunoregulatroy mechanisms reside in recognition of self MHC antigens. Autologous mixed lymphocyte reaction (AMLR) is considered to be in vitro phenomenon which reflect in vivo immune-circuit or feedback suppression. AMLR is aldo known to be abnormal in many autoimmune states. To understand further biologic significance of AMLR and to elucidate intrinsic abnormalities of self-recognition in various autoimmune diseases, we established autoreactive T cell clone, MTC-4, which arose long-term bulk cell lines repetitively stimulated with antigen tetanus toxoid (TT).
1) Helper activity of MTC-4
When MTC-4 is co-cultured with autologous non-T cells in the absence of TT or PWM, polyclonal activation is observed. The helper activity of MTC-4 is MHC-restricted in stimulatory phase, but not in effector phase. The helper activity is mediated by soluble helper factors which stimulate B cell differentiation. They are different from IL-2 and act on both small (resting) a
… More
nd large (activated) B cells.
2) Suppressor activity of MTC-4
The suppressor function of MTC-4 is elicited when they are co-cultured with autologous non-T cells pre-incubated with PWM for 4 hours. Induction of MTC-4 suppressor activity is not associated with increased proliferation of MTC-4 and is mediated by low numbers of these cells. Unlike helper function, suppression by MTC-4 is MHC-restricted in both stimulatory and effector phase. MTC-4 failed to suppress rather help MHC-mismatched allogeneic B cells even under conditions in which it manifests MHC-specific suppressor function for autologous B cells.
Thus, cloned autoreactive T cells have unique regulatory functions which depend on the kind of autologous non-T cells they interact with: 1) When stimulated by unactivated B cells, they provide helper activity; 2) When stimulated by activated B cells, they act as suppressor-effector cells. Such bi-functional property of autoreactive T cells could be important in maintaing "immunehomeostasis". It is possible that some forms of autoimmunity might result, not from the presence or absence of autreactive T cells, but rather from an imbalance in their immunoregulatory activity characterized by excessive net helper function. Less
|
Report
(2 results)
Research Products
(15 results)
