Treg and CTLA-4: two intertwining pathways to immune tolerance.
Treg and CTLA-4: two intertwining pathways to immune tolerance.
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DOI：
10.1016/j.jaut.2013.06.006
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发表时间：
2013-09
影响因子：
12.8
通讯作者：
Walker LS
中科院分区：
文献类型：
--
作者：
Walker LS
CTLA-4通路和调节性T细胞（Treg）对于控制免疫稳态都是必不可少的。它们的治疗相关性通过抗CTLA-4抗体在肿瘤治疗中的日益增加的使用以及用于自身免疫和移植环境的Treg细胞转移策略的开发而突出。1995年，随着发现Ctla-4缺陷的小鼠患有致命的淋巴组织增生综合征，CTLA-4途径首次引起免疫学界的注意。八年后，缺乏关键Treg转录因子Foxp 3的小鼠表现出非常相似的表型。大部分争论集中在Treg抑制功能是否需要CTLA-4的问题上。这一发现在某些情况下确实如此，但在另一些情况下则不然，这引起了争议，也不可避免地引起了意见的两极分化。在这篇文章中，我认为CTLA-4和Treg代表了免疫耐受的互补和很大程度上重叠的机制。我认为Treg通常使用CTLA-4来实现抑制，然而CTLA-4也可以在非Treg隔室中起作用，而Treg可以调用CTLA-4独立的抑制机制。Foxp 3和CTLA-4指导免疫调节的独立程序的概念，在实践中在很大程度上重叠，将有望帮助我们更好地理解这些途径的潜在生物学和治疗意义。CTLA-4和Treg作为免疫稳态的关键调节剂独立出现。每个途径的历史和生物学作用进行了讨论。这两种途径之间的重叠的程度和性质被认为是。
Both the CTLA-4 pathway and regulatory T cells (Treg) are essential for the control of immune homeostasis. Their therapeutic relevance is highlighted by the increasing use of anti-CTLA-4 antibody in tumor therapy and the development of Treg cell transfer strategies for use in autoimmunity and transplantation settings. The CTLA-4 pathway first came to the attention of the immunological community in 1995 with the discovery that mice deficient in Ctla-4 suffered a fatal lymphoproliferative syndrome. Eight years later, mice lacking the critical Treg transcription factor Foxp3 were shown to exhibit a remarkably similar phenotype. Much of the debate since has centered on the question of whether Treg suppressive function requires CTLA-4. The finding that it does in some settings but not in others has provoked controversy and inevitable polarization of opinion. In this article, I suggest that CTLA-4 and Treg represent complementary and largely overlapping mechanisms of immune tolerance. I argue that Treg commonly use CTLA-4 to effect suppression, however CTLA-4 can also function in the non-Treg compartment while Treg can invoke CTLA-4-independent mechanisms of suppression. The notion that Foxp3 and CTLA-4 direct independent programs of immune regulation, which in practice overlap to a significant extent, will hopefully help move us towards a better appreciation of the underlying biology and therapeutic significance of these pathways. CTLA-4 and Treg emerged independently as critical regulators of immune homeostasis. The history and biological role of each pathway is discussed. The extent and nature of the overlap between the two pathways is considered.
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影响因子：
7.7
作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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