| Project/Area Number |
11670614
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | NIIGATA UNIVERSITY |
|---|
Principal Investigator |
TANAKA Keiko NIIGATA UNIVERSITY, Brain Research Institute Department of Neurology, Associate Prof., 脳研究所, 助教授 (30217020)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUJI Shoji Niigata University, Brain Research Institute Department of Neurology, Professor, 脳研究所, 教授 (70150612)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | paraneoplastic neurological syndrome / anti-Yo antibody / anti-Hu antibody / cytotoxic T cell(CTL) / major histocompatibility antigen / T cell receptor(TCR) |
|---|
| Research Abstract |
A part of the paraneoplastic neurological syndrome could be diagnosed with characteristic anti-neuronal antibodies which also give the prediction for underlying cancer. Although these antibodies found in the sera and CSFs of patients is thought to be disease- specific, there is no direct evidence of a role in neuronal loss. Infiltration of CD8-positive T cells in the affected tissue was found in the patient with paraneoplastic cerebellar degeneration(PCD)and anti-Yo antibody or encepahlomyeloneuropathy with anti-Hu antibody(anti-Hu syndrome)which suggested HLA class I restricted cytotoxic T cells(CTL)may be involved in these disorders. First, we examined Vb genes of T cell receptors of infiltrated lymphocytes with RT-PCR and single strand conformational polym orphism method, that suggested the oligoclonal expansions of T cells in the tumor and the cerebellum/posterior ganglions of PCD/anti-Hu syndrome, respectively.
Then we examined HLA-class I- restricted cytotoxic T lymphocyte(CTL)activity against a peptid of the Yoprotein with the HLA A24-specific peptide-binding motifs or some peptides of the Hu protein with the B7 supertype-specific peptide binding motifs. CTL activity was induced in the peripheral blood of patients with PCD/anti-Hu syndrome after stimulated with specific peptides against autologous fibroblasts expressing each peptide on their surface. To clarify that CTL might really related to the neuronal damage, CTL induced animal models should be raised.
For this purpose, we immunized the mice bering common MHC motifs with these peptides and autologous dendritic cells and obtained T cell clones reactive to each peptides.
|
