Dendritic cell function in vivo during the steady state:: A role in peripheral tolerance
Dendritic cell function in vivo during the steady state:: A role in peripheral tolerance
复制标题
DOI：
10.1111/j.1749-6632.2003.tb06029.x
复制
发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Nussenzweig, M
中科院分区：
文献类型：
--
作者：
Steinman, RM;Hawiger, D;Nussenzweig, M
避免自身免疫需要主动沉默或耐受外周自身反应性 T 细胞的机制。在感染过程中，树突状细胞不仅捕获微生物抗原，还处理来自垂死细胞的自身抗原以及无害的环境蛋白质。由于树突状细胞响应微生物和其他刺激而成熟，因此有害和无害抗原都会呈递肽。因此，建立树突状细胞在感染前建立对那些自身抗原和环境抗原的耐受性的机制是有价值的，这些抗原可以在遇到病原体时进行处理。在稳定状态下，在急性感染和炎症之前，树突状细胞处于未成熟状态并且未完全分化以发挥其作为免疫诱导剂的已知作用。然而，这些未成熟的细胞并不是不活跃的。它们不断地在组织中循环并进入淋巴器官，捕获自身抗原以及无害的环境蛋白质。最近的实验提供了直接证据，表明负载抗原的未成熟树突在体内通过删除 T 细胞或通过扩增调节性 T 细胞来沉默 T 细胞。通过这种方式，建议免疫系统至少克服一些产生抗免疫和慢性炎症的风险。有人提出，树突状细胞在定义免疫学自身方面发挥着重要作用，不仅在胸腺中央，而且在外周。
The avoidance of autoimmunity requires mechanisms to actively silence or tolerize self reactive T cells in the periphery. During infection, dendritic cells are not only capturing microbial antigens, but also are processing self antigens from dying cells as well as innocuous environmental proteins. Since the dendritic cells are maturing in response to microbial and other stimuli, peptides will be presented from both noxious and innocuous antigens. Therefore it would be valuable to have mechanisms whereby dendritic cells, prior to infection, establish tolerance to those self and environmental antigens that can be processed upon pathogen encounter. In the steady state, prior to acute infection and inflammation, dendritic cells are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. These immature cells are not inactive, however. They continuously circulate through tissues and into lymphoid organs, capturing self antigens as wen as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen-loaded immature dendritic in vivo silence T cells either by deleting them or by expanding regulatory T cells. In this way, it is proposed that the immune system overcomes at least some of the risk of developing antoimmunity and chronic inflammation. It is proposed that dendritic cells play a major role in defining immunologic self, not only centrally in the thymus but also in the periphery.