T CELL VLA-4 OVEREXPRESSION IN LUPUS AND VASCULITIS

申请人提议提供资金，目的是改善目前的 血管炎发病机制中VLA-4作用的研究进展 自身免疫性疾病。这项提议也是对 申请人目前的研究情况。申请者最近证明了小鼠 转染CD18的T细胞将过度表达另一种黏附分子。 LFA-1，并成为自身反应。这些自身反应性T细胞的过继转移 细胞会在同基因小鼠中引起狼疮样自身免疫性疾病。近期 研究表明，狼疮患者的T细胞亚群也 过表达LFA-1，并具有自身反应性。有趣的是，只有狼疮患者 血管炎患者的T细胞过度表达LFA-1和VLA-4。这个 VLA-4等具有黏附功能的T细胞表面分子的作用 如CD2，在血管炎和自身免疫的发病机制中 目前尚不清楚。申请人提议使小鼠T细胞 过度表达VLA-4和CD2，同时存在和不存在LFA-1 过表达，通过转基因实验。其体外意义的研究进展 VLA-4和CD2过表达对T细胞自身反应性和T细胞黏附的影响 我们将探索其功能。体外试验的体内意义 变化将通过采用迁移实验来确定。 首席调查员正在申请作为独立新闻工作者的支持 调查员。应聘者最近担任了终身教职跟踪职位 老年风湿科助理教授 1996年12月在密歇根大学。

The applicant proposes funding with the intent of improving the current understanding of the role of VLA-4 in the pathogenesis of vasculitis in autoimmune diseases. The proposal ius also a natural extension of the applicant's current research. The applicant has recently shown that murine T cells transfected with CD18 will overexpress another adhesion molecule., LFA-1, and become autoreactive. Adoptive transfer of these autoreactive T cells causes a lupus-like autoimmune disease in syngeneic mice. Recent study has shown that a subset of T cells from lupus patients also overexpress LFA-1 and are autoreactive. Interestingly, only lupus patients with vasculitis have T cells that overexpress both LFA-1 and VLA-4. The role of VLA-4, and other T cell surface molecules with adhesion function such as CD2, in the pathogenesis of vasculitis and autoimmunity is currently unknown. The applicant proposes to cause murine T cells to overexpress VLA-4 and CD2, with and without concurrent LFA-1 overexpression, by transfection experiments. The in vitro significance of VLA-4 and CD2 overexpression of T cell autoreactivity and T cell adhesion functions will be explored. The in vivo significance of the in vitro changes will then be determined by adoptive transfer experiments. The principal investigator is applying for support as an independent new investigator. The applicant has recently assumed a tenure track position as an Assistant Professor in the Division of Geriatrics and Rheumatology at the university of Michigan in December, 1996.