Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
J Exp Med. 2013 Jun 3;210(6):1167-78. doi: 10.1084/jem.20122462. Epub 2013 May 6.
The emergence of the adaptive immune system took a toll in the form of pathologies mediated by self-reactive cells. Regulatory T cells (T reg cells) exert a critical brake on responses of T and B lymphocytes to self- and foreign antigens. Here, we asked whether T reg cells are required to restrain NK cells, the third lymphocyte lineage, whose features combine innate and adaptive immune cell properties. Although depletion of T reg cells led to systemic fatal autoimmunity, NK cell tolerance and reactivity to strong activating self- and non-self-ligands remained largely intact. In contrast, missing-self responses were increased in the absence of T reg cells as the result of heightened IL-2 availability. We found that IL-2 rapidly boosted the capacity of NK cells to productively engage target cells and enabled NK cell responses to weak stimulation. Our results suggest that IL-2-dependent adaptive-innate lymphocyte cross talk tunes NK cell reactivity and that T reg cells restrain NK cell cytotoxicity by limiting the availability of IL-2.
适应性免疫系统的出现带来了自身反应性细胞介导的病理学问题。调节性 T 细胞（Treg 细胞）对 T 和 B 淋巴细胞对自身和外来抗原的反应起着关键的刹车作用。在这里，我们想知道 Treg 细胞是否需要抑制 NK 细胞，NK 细胞是第三淋巴细胞谱系，其特征结合了先天和适应性免疫细胞的特性。尽管 Treg 细胞耗竭导致全身性致命自身免疫，但 NK 细胞对强激活自身和非自身配体的耐受和反应性基本保持完整。相比之下，由于 IL-2 可用性增加，在没有 Treg 细胞的情况下，缺失自我反应增加。我们发现，IL-2 可迅速增强 NK 细胞与靶细胞有效结合的能力，并使 NK 细胞对弱刺激产生反应。我们的结果表明，IL-2 依赖性适应性-先天淋巴细胞交叉对话调节 NK 细胞的反应性，而 Treg 细胞通过限制 IL-2 的可用性来抑制 NK 细胞的细胞毒性。
