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Selective Suppression of Pathogenic T Cell Responses Using Dendritic Cells

使用树突状细胞选择性抑制致病性 T 细胞反应

基本信息

批准号：
09307011
负责人：
IKEDA Yasuo
金额：
$ 18.5万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A).
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

项目摘要

Dendritic cells (DC) are Antigen-presenting cells that are essential for initiation of T cell-dependent immunity, but distinct DC subsets are known to direct different classes of immune responses. Lymphoid DC precursors (pDC2) or plasmacytoid DC were recently identified as a human DC subset producing type I interferon and skewing Th2 responses. Here, we demonstrate that pDC2 isolated from human peripheral blood have a capacity to induce an anergic state in antigen-specific CD4^+ T cell lines. Tetanus toxoid (TT)-specific T cells incubated with TT-pulsed autologous pDC2 failed to proliferate in secondary cultures with optimal antigenic stimulation. T cell anergy induction required T cell receptor engagement with antigen/major histocompatibility complex presented on pDC2. The pDC2-induced unresponsiveness was completely or partially reversible in the presence of high-dose IL-2 in the secondary cultures. Autoreactive CD4^+ T cell clones specific for topoisomerase I derived from a patient with scleroderma were rendered anergic after coculture with topoisomerase I-pulsed autologous pDC2, resulting in failure to proliferate or provide help to B cells. These results suggest that pDC2 are involved in maintenance of peripheral T cell tolerance and have potential for use in the suppression of pathogenic T cell responses in autoimmune diseases and organ transplantation.

树突状细胞（DC）是抗原呈递细胞，其对于T细胞依赖性免疫的起始是必需的，但已知不同的DC亚群指导不同类别的免疫应答。类浆细胞DC前体（pDC 2）或浆细胞样DC最近被鉴定为产生I型干扰素和偏斜Th 2应答的人DC亚群。在这里，我们证明了从人外周血中分离的pDC 2具有诱导抗原特异性CD 4 ^+ T细胞系的无能状态的能力。破伤风类毒素（TT）-特异性T细胞与TT-脉冲自体pDC 2孵育未能增殖的第二次培养物与最佳的抗原刺激。T细胞无能诱导需要T细胞受体与pDC 2上呈递的抗原/主要组织相容性复合物接合。在二级培养物中存在高剂量IL-2的情况下，pDC 2诱导的无反应性完全或部分可逆。从硬皮病患者中分离出的对拓扑异构酶I具有特异性的自身反应性CD 4 ^+ T细胞克隆在与拓扑异构酶I致敏的自体pDC 2共培养后变得无反应性，导致不能增殖或不能为B细胞提供帮助。这些结果表明，pDC 2参与维持外周T细胞耐受性，并有可能用于抑制自身免疫性疾病和器官移植中的致病性T细胞应答。