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2. 发明申请

WO2008098787A3 CD83 AS A MOLECULAR SWITCH FOR THE INDUCTION OF REGULATORY (IMMUNOSUPPRESSIVE) T-CELLS 审中-公开
标题翻译： CD83作为诱导调控（免疫抑制）T细胞的分子开关
公开(公告)号：WO2008098787A3
公开(公告)日：2008-11-13
申请号：PCT/EP2008001186
申请日：2008-02-15
申请人： HELMHOLTZ INFEKTIONSFORSCHUNG , HANSEN WIEBKE , BUER JAN , REINWALD SIMONE
发明人： HANSEN WIEBKE , BUER JAN , REINWALD SIMONE
IPC分类号： G01N33/68
CPC分类号： G01N33/56972 , C07K14/70503 , G01N33/505 , G01N33/564 , G01N2333/70596 , G01N2500/00 , G01N2800/24
摘要： The present invention makes use of the role of the surface protein CD83 in the induction of regulatory T cells (Tregs). The present invention relates to means and methods for overexpressing CD83 as well as methods for identifying compounds that are interacting with the CD83 polypeptide, and to compounds capable of functioning as immunomodulators in mammals, in particular humans. In addition, the present invention relates to methods of treatment of a subject, in particular a human, suffering from an undesired immunoreaction. The transmembrane protein CD83 has been initially described as a maturation marker for dendritic cells (DCs). Moreover, there is increasing evidence that CD83 also regulates B cell function, thymic T cell maturation and peripheral T cell activation. Here, we show that CD83 expression confers immunosuppressive function to CD4 + T cells. CD83 mRNA is differentially expressed in naturally occurring CD4 + CD25 + regulatory T (Treg) cells and upon activation these cells rapidly express large amounts of surface CD83. Transduction of naive CD4 + CD25 - T cells with CD83 encoding retroviruses induces a regulatory phenotype in vitro, which is accompanied by the induction of Foxp3. Functional analysis of CD83-transduced T cells in vivo demonstrates that these CD83 + Foxp3 + T cells are able to interfere with the effector phase of severe contact hypersensitivity (CHS) reaction of the skin. Moreover, adoptive transfer of these cells prevents the paralysis associated with experimental autoimmune encephalomyelitis (EAE), suppresses pro-inflammatory cytokines IFN- and IL- 17 and increases anti-inflammatory IL-IO in recipient mice. Together, our data provides the first evidence that CD83 expression can contribute to the immunosuppressive function of CD4 + T cells in vivo.
摘要翻译：本发明利用表面蛋白CD83在诱导调节性T细胞（Treg）中的作用。本发明涉及用于过表达CD83的手段和方法以及用于鉴定与CD83多肽相互作用的化合物的方法，并且涉及能够在哺乳动物特别是人中用作免疫调节剂的化合物。另外，本发明涉及治疗患有不希望的免疫反应的受试者，特别是人的方法。跨膜蛋白CD83最初被描述为树突细胞（DC）的成熟标记。此外，越来越多的证据表明CD83还调节B细胞功能，胸腺T细胞成熟和外周T细胞活化。在这里，我们显示CD83表达赋予CD4 + + T细胞免疫抑制功能。 CD83 mRNA在天然存在的CD4 + / CD25 + /调节性T（Treg）细胞中差异性表达，并且在活化后，这些细胞迅速表达大量的表面CD83。原代CD4 + CD25 + T细胞与CD83编码逆转录病毒的转导在体外诱导调节表型，其伴随着Foxp3的诱导。体内CD83转导的T细胞的功能分析表明这些CD83 + Foxp3 + T细胞能够干扰严重接触过敏（CHS）反应的效应物阶段皮。此外，这些细胞的过继转移防止了与实验性自身免疫性脑脊髓炎（EAE）相关的麻痹，抑制了受体小鼠中的促炎细胞因子IFN-和IL-17并增加了抗炎IL-10。总之，我们的数据提供了CD83表达可以促进体内CD4 + / T细胞的免疫抑制功能的第一个证据。

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