Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells
Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells
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DOI：
10.1182/blood-2002-09-2712
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发表时间：
2003-05-01
期刊：
影响因子：
20.3
通讯作者：
Matsuyama, T
中科院分区：
文献类型：
--
作者：
Sato, K;Yamashita, N;Matsuyama, T
为了开发调节T细胞介导的免疫的新策略，我们建立了具有有效免疫调节特性的人和鼠修饰树突状细胞（DC）（设计为调节性DC），与正常对应物相比，其显示出中等高水平的主要组织相容性复合体（MHC）分子的表达水平和极低水平的共刺激分子。与引起同种异体 CD4+ 和 CD8+ T 细胞激活的人类正常 DC 不同，人类调节性 DC 不仅诱导其无能状态，而且在体外从各自的初始亚群中产生 CD4+ 或 CD8+ 调节性 T (Tr) 细胞。尽管小鼠正常 DC 在体外激活人类异种反应性 T 细胞，但小鼠调节性 DC 会诱导其反应性低下。此外，将经引发的人类 T 细胞与小鼠正常 DC 移植到严重联合免疫缺陷 (SCID) 小鼠中的效果得到增强。异种移植物抗宿主病（XGVHD）引起的致死率，而用小鼠调节性 DC 移植已引发的人类 T 细胞会削弱其引起 XGVHD 的能力。此外，异种或同种异体移植后单次注射小鼠调节性树突状细胞可以保护受体免受XGVHD以及同种异体急性GVHD引起的死亡。因此，调节性 DC 对 T 细胞介导的免疫的调节为免疫性疾病提供了一种新的治疗方法。 (C) 2003 年，美国血液学会。
To exploit a novel strategy to regulate T cell-mediated immunity, we established human and murine modified dendritic cells (DCs) with potent immunoregulatory properties (designed as regulatory DCs), which displayed moderately high expression levels of major histocompatibility complex (MHC) molecules, and extremely low levels of costimulatory molecules compared with their normal counterparts. Unlike human normal DCs, which caused the activation of allogeneic CD4(+) and CD8(+) T cells, human regulatory DCs not only induced their anergic state but also generated CD4(+) or CD8(+) regulatory T (Tr) cells from their respective naive subsets in vitro. Although murine normal DCs activated human xenoreactive T cells in vitro, murine regulatory DCs induced their hyporesponsiveness. Furthermore, transplantation of the primed human T cells with murine normal DCs into severe combined immunodeficient (SCID) mice enhanced. the lethality caused by xenogeneic graft-versus-host disease (XGVHD), whereas transplantation of the primed human T cells with murine regulatory DCs impaired their ability to cause XGVHD. In addition, a single injection of murine regulatory DCs following xenogeneic or allogeneic transplantation protected the recipients from the lethality caused by XGVHD as well as allogeneic acute GVHD. Thus, the modulation of T cell-mediated immunity by regulatory DCs provides a novel therapeutic approach for immunopathogenic diseases. (C) 2003 by The American Society of Hematology.