| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
To understand the pathomechanisms of autoimmune skin disesase, CD8 positive T cells from the chicken ovalubumin (OVA) specific T cell receptor transgenic mice (OT-1 Tg mice) were transferred into the K14-mOVA Tg mice, which express model antigen (OVA) on the surface of epidermal keratinocytes. In addition, OT-1 T cells were transferred into the OT-1 x K14-mOVA double transgenic mice, and phenotypical change of the skin and lymph nodes was analysed.
After the transfer of OT-1 T cells, K14-mOVA Tg mice were loosing their wight, and induced GVHD like skin lesions. Flow cytometric analysis of the superficial lymph node cells demonstrated the activating phenotype. In contrast, neither body weight loss nor skin change was induced in the doubleTg mice after the OT-1 T cell transfer, suggesting the presence of the inhibitory mechanism in the double Tg mice.
When double Tg mice were pretreated with anti CD3 or CD4 monoclonal antibodies, GVHD like skin lesions were developed after the OT-1 T cell
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transfer. In contrast, no skin lesions were developed if the double Tg mice were pretreated with anti CD8 or CD25 monoclolan antibodies before OT-1 T cell transfer. These results indicate that the inhibitory mechanism observed in doble Tg mice were mediated by CD3 and/or CD4 T cells.
To more precisely define the cell population responsible for this inhibitory mechanism, the lymph node cells in double Tg mice were analysed by flowcytometory. Compared with the wild type controls, the ratio of the CD3+,CD4-,CD8- cells was significantly increased in the double Tg mice. If the CD3+,CD4-,CD8- cell fraction was prepared from the double Tg mice, and co-cultured with OT-1 T cells in the presence of OVA, significantly reduced proliferation response was observed..
These results indicate that the CD3+,CD4-,CD8- cell population present in the lymph nodes actively inhibit the T cell activation both in vitro and in vivo. Further characterization of the inhibitory mechanism observed in double Tg mice may lead to the elucidation of the pathomechanisms, and the development of the new therapeutic modalities of the autoimmune diseases. Less
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