Differentiation of T regulatory cells by immature dendritic cells.
Differentiation of T regulatory cells by immature dendritic cells.
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DOI：
10.1084/jem.193.2.f5
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发表时间：
2001-01-15
影响因子：
15.3
通讯作者：
Traversari, C
中科院分区：
文献类型：
--
作者：
Roncarolo, M G;Levings, M K;Traversari, C
诱导抗原特异性耐受对于预防自身免疫和维持免疫稳态至关重要。免疫系统区分自身和非自身以及无害和有害外来抗原的能力由中枢和外周耐受机制控制。中枢耐受是一种完善的机制，涉及在胸腺中与骨髓来源的树突状细胞 (DC) 相互作用时删除自身反应性 T 细胞 (1, 2)。外周耐受的明确特征机制包括诱导细胞死亡或形成 T 细胞无反应（无反应）状态 (3, 4)。此外，调节性 T (Tr) 细胞的主动抑制也是外周耐受的关键 (5)。然而，Tr 细胞在体内产生并发挥其免疫调节作用的机制仍有待确定，并且是深入研究的主题。DC 在诱导外周耐受中的作用已得到多项研究的支持 (6, 7)。目前，负责这一过程的机制尚不清楚(8)。然而，人们普遍认为，在存在自体/无害抗原的情况下，控制 DC 的成熟/激活状态 (7) 和/或 DC 的亚型 (9, 10) 对于诱导外周耐受至关重要。两篇论文，一篇由 Jonuleit 等人撰写。 11 月 6 日刊 (11) 以及 Dhodapkar 等人的一篇。在本期（12）中，强烈建议未成熟的 DC（iDC）可能通过诱导人 Tr 细胞的分化来控制外周耐受。
The induction of antigen-specific tolerance is critical for the prevention of autoimmunity and maintenance of immune homeostasis. The immune system’s ability to distinguish between self and non-self and between innocuous and harmful foreign antigens is controlled by mechanisms of central and peripheral tolerance. Central tolerance is a well established mechanism that involves deletion of selfreactive T cells upon interaction with bone marrow–derived dendritic cells (DCs) in the thymus (1, 2). Well characterized mechanisms of peripheral tolerance include the induction of cell death or the development of a state of nonresponsiveness (anergy) of T cells (3, 4). In addition, active suppression by T regulatory (Tr) cells is also key for peripheral tolerance (5). However, the mechanisms by which Tr cells arise in vivo and exert their immunoregulatory effects remain to be defined and are the subject of intensive investigation.A role for DCs in the induction of peripheral tolerance has been supported by several studies (6, 7). At present, the mechanisms responsible for this process are not clear (8). However, it is widely assumed that, in the presence of self/harmless antigens, control of the maturation/activation state of DCs (7), and/or the subtype of DCs (9, 10) is fundamental in the induction of peripheral tolerance. Two papers, one by Jonuleit et al. in the November 6 issue (11) and one by Dhodapkar et al. in this issue (12), strongly suggest that immature DCs (iDCs) may control peripheral tolerance by inducing the differentiation of human Tr cells.