| Project/Area Number |
10470123
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMAMOTO Kazuhiko University of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (80191394)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOHARA Satoshi University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (90282657)
DOHI Makoto University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (60222155)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 1999: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1998: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | Autoimmune diseases / antigen-specific T cells / T cell receptor / T cell clone / rheumatoid arthritis / systemic lupus erythematosus / T細胞クローン / 全身エリテマトーデス / 皮膚筋炎・多発筋炎 / リコンビナント抗原 |
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| Research Abstract |
The involvement of antigen-specific T cells in the pathogenesis of systemic types of autoimmune disorders is still controversial. Essentially, activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Therefore, it is crucial to detect such T cells in order to know the contribution of antigen -specific immune responses in the diseases. However, the methods available to analyze T cell clonality are still limited. In this respect, we have established a novel method using a combination of reverse transcriptase-polymerase chain reaction of T cell receptor beta chain transcripts and single strand conformation polymorphism (SSCP). Using this method, the dynamic changes of T cell clonal responses during an antigenic stimulation could be monitored. Analyses of several autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus and their animal models, revealed the involvement of antigen specific T cell immune responses. Furthermore, taking advantage of the reproducible mobility of a band in SSCP gel, we are now able to compare identities of the accumulated T cell clones in different samples Without the need for nucleotide sequencing of each clone. Such information can thus elucidate the occurrence of uniform or stable immunological reactions in the patients and also suggests that these reactions play an important role in the pathogenesis. Developing this system, we are also establishing a new strategy to determine the antigen specificities of these in vivo accumulating T cell clones.
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