Autoaggressive CD8 T cells in polymyositis
| Project/Area Number |
13670452
|
|---|
| 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 | Tokyo Medical & Dental University |
|---|
Principal Investigator |
KOHSAKA Hitoshi Tokyo Medical and Dental University, Graduate School, Department of Bioregulatpry Medicine and Rheumatology, Associate professor., 大学院・医歯学総合研究科, 助教授 (00251554)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIYASAKA Nobuyuki Tokyo Medical and Dental University, Graduate School, Department of Bioregulatory Medicine and Rheumatology, Professor, 大学院・医歯学総合研究科, 教授 (30157622)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Keywords | polymiositis / CD8T cells / autoimmunity |
|---|
| Research Abstract |
Polymyositis (PM) involves destruction of striated muscles by autoaggressive CD8 T cells, which accumulate and secrete cytotoxic effecter molecules in the affected muscles. On the other hand, studies of peripheral T cell repertoires from normal individuals and patients with viral infections have shown that primed CD8 T cells, unlike CD4 T cells are prone to expand clonally and persist as large populations in the peripheral blood. This made us assume that autoaggressive myocytotoxic CD8 T cells would be expanded clonally in the peripheral blood from patients with PM. By clonal analyzes of peripheral T cells from patients and age-matched controls, we show here that clonal expansion of CD8 T cells, but not that of CD4 T cells, was significantly more frequent in patients. In analogy to virus-specific T cells, the expanded T cells persisted as large populations over time. Analysis of the muscle biopsy specimens revealed that some of the expanded clones were infiltrating in the affected muscles from the same patients. These results provide the first evidence that local autoimmune reaction directly elicits significant biases in peripheral T cell repertoire. Since the expanded cells, which should be candidate autoaggressive T cells, are readily isolated from peripheral blood, our findings should give us an immediate clue to analysis of the pathogenic T cells in PM.
Following studies failed to show that the expanded cells recognize human C-protein that is responsible for a rodent model of PM. The future studies will be focused on the antigen specificity of the expanded cells.
|
Report
(3 results)
Research Products
(6 results)
