Division of Respirology and Clinician-Scientist Training Program, Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
J Mol Cell Biol. 2012 Feb;4(1):48-58. doi: 10.1093/jmcb/mjr043.
T lymphocytes bearing the αβ T cell receptor (TCR) but lacking CD4, CD8, and markers of natural killer (NK) cell differentiation are known as 'double-negative' (DN) T cells and have been described in both humans and rodent models. We and others have shown that DN T cells can act as regulatory T cells (Tregs) that are able to prevent allograft rejection, graft-versus-host disease, and autoimmune diabetes. In the last few years, new data have revealed evidence of DN Treg function in vivo in rodents and humans. Moreover, significant advances have been made in the mechanisms by which DN Tregs target antigen-specific T cells. One major limitation of the field is the lack of a specific marker that can be used to distinguish truly regulatory DN T cells (DN Tregs) from non-regulatory ones, and this is the central challenge in the coming years. Here, we review recent progress on the role of DN Tregs in transplantation and autoimmunity, and their mechanisms of action. We also provide some perspectives on how DN Tregs compare with Foxp3(+) Tregs.
表达 αβ T 细胞受体（TCR）但缺乏 CD4、CD8 和自然杀伤（NK）细胞分化标志物的 T 淋巴细胞被称为“双阴性”（DN）T 细胞，在人类和啮齿动物模型中均有描述。我们和其他人已经表明，DN T 细胞可以作为调节性 T 细胞（Tregs），能够预防同种异体移植物排斥、移植物抗宿主病和自身免疫性糖尿病。在过去的几年中，新的数据揭示了 DN Treg 在体内在啮齿动物和人类中发挥作用的证据。此外，DN Tregs 靶向抗原特异性 T 细胞的机制方面取得了重大进展。该领域的一个主要限制是缺乏可用于区分真正的调节性 DN T 细胞（DN Tregs）和非调节性 DN T 细胞的特异性标记物，这是未来几年的核心挑战。在这里，我们回顾了 DN Tregs 在移植和自身免疫中的作用及其作用机制的最新进展。我们还就 DN Tregs 与 Foxp3(+) Tregs 的比较提供了一些观点。
