公开(公告)号：US20060127400A1

公开(公告)日：2006-06-15

申请号：US11346938

申请日：2006-02-03

申请人： Andrew Taylor ,  Tomomi Nishida

发明人： Andrew Taylor ,  Tomomi Nishida

IPC分类号： A61K39/395 ,  C12P21/04 ,  C12N5/06

CPC分类号： A61K38/34 ,  A61K39/0008 ,  A61K2035/122 ,  C12N5/0636 ,  C12N2500/90 ,  C12N2501/15 ,  C12N2501/515 ,  C12N2501/86 ,  C12N2510/00

摘要： The invention encompasses a method of down-regulating a T cell-mediated immune response, through activation or T cell receptor (TCR) stimulation of antigen-primed T cells in the presence of alpha-melanocyte stimulating hormone (α-MSH), which may be optionally enhanced by adding transforming growth factor-β2 (TGF-β2) approximately 4-6 hours after the start of the primed T cells' exposure to α-MSH. Activation of the primed T cells may be mediated by presentation of the specific antigen to the primed T cells, or by an anti-TCR antibody or a T cell mitogen. As a result of the α-MSH treatment modulating the T cell activation, antigen-specific, regulatory, CD4+/CD25+ T cells are generated that produce transforming growth factor-β (TGF-β) and can non-specifically down-regulate Th1-mediated inflammatory activities. The method may be used to down-regulate or suppress an autoimmune condition or a graft rejection in a transplant patient. The invention also encompasses a kit for generating regulatory T cell comprising a specific antigen, α-MSH, and optionally, TGF-β2 and/or a T cell culture medium. Also provided are gene therapy treatments for suppressing an autoimmune or graft rejection response, or for re-establishing autotolerance, by introducing genetic material (e.g. nucleic acid) for expressing α-MSH or a receptor-binding portion thereof, into a localized tissue site.

摘要翻译： 本发明包括通过在α-黑素细胞刺激激素（α-MSH）的存在下通过激活或T细胞受体（TCR）刺激抗原引发的T细胞来降低T细胞介导的免疫应答的方法，其可以 任选地通过在引发的T细胞暴露于α-MSH开始后约4-6小时加入转化生长因子-β2（TGF-β2）来增强。 引发的T细胞的活化可以通过将特异性抗原呈递给引发的T细胞或通过抗TCR抗体或T细胞丝裂原来介导。 由于α-MSH处理调节T细胞活化的结果，产生产生转化生长因子-β（TGF-β）的抗原特异性，调节性CD 4 + / CD 25 + T细胞，并且可以非特异性地下调 调节Th1介导的炎症活动。 该方法可用于下调或抑制移植患者中的自身免疫病症或移植排斥反应。 本发明还包括用于产生包含特异性抗原α-MSH和任选的TGF-β2和/或T细胞培养基的调节性T细胞的试剂盒。 还提供了通过将用于表达α-MSH或其受体结合部分的遗传物质（例如核酸）引入局部组织部位来抑制自身免疫或移植排斥反应或重建自身耐受性的基因治疗治疗。