IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis
IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis
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DOI：
10.1182/blood-2011-10-388546
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发表时间：
2012-05-17
期刊：
影响因子：
20.3
通讯作者：
Walker, Lucy S. K.
中科院分区：
文献类型：
--
作者：
Attridge, Kesley;Wang, Chun Jing;Walker, Lucy S. K.
调节性T细胞（Treg）抑制的调节对于疫苗开发、肿瘤监测的有效性和自身免疫的出现具有重要意义。我们先前已经表明，细胞因子IL-21可以抵消Treg抑制。然而，这是否反映了IL-21对Treg、常规T细胞或抗原呈递细胞的作用尚不清楚。在这里，我们使用来自IL-21R缺陷小鼠的淋巴细胞群来确定IL-21需要靶向哪种细胞类型以克服Treg抑制。我们发现IL-21通过作用于常规T细胞来抵消抑制，并且这与IL-2产生的抑制有关。尽管缺乏IL-2，但常规T细胞应答不受损害，因为IL-21可以替代IL-2作为T细胞生长因子。然而，IL-21不能替代IL-2支持Treg区室。因此，常规T细胞中的IL-21信号传导通过降低IL-2可用性间接影响Treg稳态。这些数据表明，IL-21和IL-2在促进常规T细胞应答中可能具有重叠的作用，但在控制Treg稳态和功能中发挥不同的作用。这些数据还表明了一种新的范例，即细胞因子可以通过抑制IL-2来促进免疫。（血。2012; 119（20）：4656 - 4664）
Modulation of regulatory T cell (Treg) suppression has important implications for vaccine development, the effectiveness of tumor surveillance, and the emergence of autoimmunity. We have previously shown that the cytokine IL-21 can counteract Treg suppression. However, whether this reflects an effect of IL-21 on Treg, conventional T cells, or antigen-presenting cells is not known. Here we have used lymphocyte populations from IL-21R-deficient mice to pinpoint which cell type needs to be targeted by IL-21 for Treg suppression to be overcome. We show that IL-21 counteracts suppression by acting on conventional T cells and that this is associated with inhibition of IL-2 production. Despite the lack of IL-2, conventional T-cell responses proceed unimpaired because IL-21 can substitute for IL-2 as a T cell growth factor. However, IL-21 is unable to substitute for IL-2 in supporting the Treg compartment. Thus, IL-21 signaling in conventional T cells indirectly impacts Treg homeostasis by decreasing IL-2 availability. These data demonstrate that IL-21 and IL-2 can have overlapping roles in promoting conventional T-cell responses but play distinct roles in controlling Treg homeostasis and function. The data also suggest a new paradigm whereby cytokines can promote immunity by inhibiting IL-2. (Blood. 2012; 119(20): 4656-4664)