Molecular mechanism for homing of T cells to the epidermis
| Project/Area Number |
04454288
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Kyorin University School of Medicine |
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Principal Investigator |
SHIOHARA Tetsuo Kyorin University School of Medicine, Dept.of Dermatology, Associate Professor, 医学部, 助教授 (10118953)
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| Co-Investigator(Kenkyū-buntansha) |
KOMATSU Takehiko Kyorin University School of Medicine, Dept.of Dermatology, Instructor0, 医学部, 助手 (60162046)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | Dendritic epidermal cells (dEC) / T cell receptor (TCR)alphabeta / Bone marrow cells / Fixed drug eruption (FDE) / TCRTCR Valpha-Vbeta gene usage / RT-PCR / CLA / Adhesion molecules / TCR Valpha・Vbeta遺伝子 / 表皮内T細胞 / LFA-1 / 自己反応性T細胞 / GvH病 / αβ型T細胞レセプター / 細胞傷害活性 / PCR法 |
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| Research Abstract |
Although earlier studies suggested that in mice homing of T cells to the epidermis is a unique property of Vgamma5^+ fetal thymocytes, we demonstrated that adult bone marrow (BM) cells migrate into the epidermis and differentiate there into T cell receptor (TCR)-alphabeta^+ CD8^+ dendritic epidermal cells (dEC), a phenotype not previously demonstrated in dEC.We further demonstrated that adult thymocytes also migrate to the epidermis and give rise to TCR-alphabeta^+ CD8^+ dEC.However, our failure to analyze TCR repertoire of these TCR-alphabeta^+ CD8^+ dEC by RT-PCR method prevented us from determining whether expression of particular TCR could be required for the homing of these T cells to the epidermis.
We next took an alternative approach, Based on the previous suggestion that disease with selective destruction of epethelia may be mediated by T cells indigenously residing in epithelial tissue, such as dEC : In this regard, fixed drug eruption (FDE) appeared to have unique features best suited for analyzes of epidermal T cells ; T cells were prepared from the lesional epidermis in patients with FDE a long period after clinical resolution and their TCR repertoire and expression of adhesion molecules were examined. Comparative analyzes of TCR Valpha and Vbeta expression in the epidermal T cells and the paired PBL by quantitative RT-PCR demonstrated that TCR Valpha and Vbeta gene usage of the epidermal T cells is very restricted and that the restriction is much more apparent in those isolated from the lesion after multiple episodes. These results indicate that epidermal homing of the T cells may not be determined by particular TCR specificities but expansion of epideermal T cells with particular TCR would occur in situ after multiple episodes. Because these epidermal T cells have the much higher LFA-1 and CLA levels as compared with PBL, the high level expression of these molecules may be determinative of epidermal homing of certain T cells.
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Report
(3 results)
Research Products
(19 results)
