Molecular immunological investigation of Vogt-Koyanagi-Harada disease

Research Project

Project/Area Number	13671818
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Ophthalmology
Research Institution	AKTTA UNIVERSITY
Principal Investigator	YAMAKI Kunihiko Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (20125751)
Co-Investigator(Kenkyū-buntansha)	KONNNO Seiki Akita University, School of Medicine, Research Associate, 医学部, 助教授 (00312710) SAKURAGI Shozo Akita University, School of Medicine, Professor, 医学部, 教授 (80006767)
Project Period (FY)	2001 – 2002
Project Status	Completed (Fiscal Year 2002)
Budget Amount *help	¥3,500,000 (Direct Cost: ¥3,500,000) Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords	T cell clone / Tyrosinase family proteins / VKH disease / animal model / Tyrosinase TRP1 / CD4 T cell(Th1 cell) / TCRCT cell receptor
Research Abstract	We had established animal model of Vogt-Koyanai-Harada (VKH) disease. This model was induced by immunization of tyrosinase family proteins and the histologie findings of this disease was almost identical to that of human VKH disease. We had done lymphocyte proliferation assay against tyrosinase family proteins using PBMC of acute and untreated stage of VKH disease patients. These lymphocytes showed proliferative response against one or more of the peptides derived from tyrosinase and/or TRP1. From these facts, we proposed taht the target antigens of VKH disease are tyrosinase family proteins. Then, we established T cell clone from PBMC of the YKH disease patients. The TCCs from VKH disease patients showed reactivity against the peptides that can interact with the HLA BRB1*0405. These TCCs were Th1 cells and may play important role to the induction of the disease. Finally, we established TCCs from aqueous humors and cerebrospinal fluid (CSF) of VKH disease patients. We could establish TCCs from 7 of the fresh and untreated stage of VKH disease patients. Many TCCs were established and 30 clones, 21 from aqueous humor and 9 from CSF were tested the reactivity against tyrosinase family proteins. Surprisingly, 10/21 of TCCs from aqueous humor and 2/9 of TCCs from CSF showed proliferative response against tyrosinase or TRP1. These ratios were very high. We are now analyzing the T cell receptor (TCR) with RT-PCR SSCP. These methods may reveal the T cells that cause the autoimmune disease.