Project/Area Number |
10670810
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
|
Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
MIZOGUCHI Masako Professor & Director, Dept of Dermatol, St.Marianna Univ., 医学部, 教授 (30010250)
|
Co-Investigator(Kenkyū-buntansha) |
西岡 久寿樹 聖マリアンナ医科大学, 難病治療研究センター, 教授 (60049070)
河 陽子 聖マリアンナ医科大学, 医学部, 助手 (10082273)
TAKAHAMA Hideto Assistant, Dept of Dermatol, St.Marianna Univ., 医学部, 助手 (90267633)
KUSUKI Nishioka Professor & Director, Institute of Medical Science, St.Marianna Univ.
YOKO Kawa Assistant, Dept of Dermatol, St.Marianna Univ.
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
Keywords | Atopic Dermatitis / T cell clone / T cell receptor / RT-PCR / SSCP / Dermatophagoides pteronycsinus(Dp) |
Research Abstract |
Involvement of T cell-mediated immune response, especially that toward the house dust mite (HDM) antigens, has been suggested in atopic dermatitis (AD). Although oligoclonal T cell accumulation in the skin lesion of AD has been observed, the exact target antigen in vivo has not been identified. We here investigated whether such skin-infiltrating T cells clones recognize HDM by analyzing T cell receptor (TCR) B genes. Specifically, peripheral blood mononuclear cells (PBMC) obtained from six AD patients, who showed high anti-HDM IgE titer, were cultured with HDM antigens purified from Dermatophagoides pteronyssinus (Dp). TCR B genes of the HDM-stimulated T cells in vitro were analyzed by the combination of reverse transcription polymerase chain reaction (RT-PCR) and subsequent single strand comformation polymorphism (SSCP) methods and then compared to that of T cells accumulated in the AD skin lesion in vivo. Nucleotide sequences of the TCR were also determined. Dp stimulation induce oligoclonal T cell expansion from the originally heterogeneous peripheral T cell population of AD patients. Moreover, several Dp-responding T cell clones were identical to the in vivo accumulating clones in the AD skin lesion, indicating the antigen-specific clonal accumulation of the skin-infiltrating T cells. These findings first demonstrated that the clonally accumulating T cells in the AD skin lesion, at least in part, are actually recognizing the Dp antigen in vivo as a specific target of their cellular immune response. Targeting of such T cells may lead to antigen-specific therapy for AD.
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