Regulatory T Cells Maintain Selective Access to IL-2 and Immune Homeostasis despite Substantially Reduced CD25 Function.
Regulatory T Cells Maintain Selective Access to IL-2 and Immune Homeostasis despite Substantially Reduced CD25 Function.
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调节性T细胞保持对IL-2和免疫稳态的选择性接近，尽管CD 25功能显著降低。
DOI：
10.4049/jimmunol.1901520
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发表时间：
2020-11-15
期刊：
影响因子：
--
通讯作者：
Campbell DJ
中科院分区：
文献类型：
--
作者：
Hayes ET;Hagan CE;Khoryati L;Gavin MA;Campbell DJ
白介素2(IL-2)通过影响调节性T细胞(Treg)和效应性T细胞(TJeff)，是免疫稳态的重要调节因子。然而，IL-2在成人外周免疫系统中Treg细胞的维持和功能中的确切作用尚不清楚。在这里，我们报道，在小鼠中和IL-2可以取消Treg细胞中的所有IL-2受体信号，但耐受性良好，并且仅逐渐影响Treg细胞的功能和免疫稳态。相比之下，尽管显著降低了IL-2的敏感性，Treg细胞仍保持着选择性的IL-2信号，并在使用抑制性抗CD25抗体PC61治疗后防止了免疫失调。用同一CD25抗体的耗竭版本减少Treg细胞允许CD8+Tef增殖，然后发展为更广泛的免疫失调。因此，尽管CD25的表达和功能受到严重抑制，Treg细胞仍能选择性地获得支持其体内抗炎功能的IL-2。抗体介导的CD25靶向正被积极应用于自身免疫性疾病的治疗和预防同种异体移植排斥反应，我们的发现有助于为治疗操作和设计最佳患者结果提供信息。
Interleukin-2 (IL-2) is a critical regulator of immune homeostasis through its impact on both regulatory T (Treg) and effector T (Teff) cells. However, the precise role of IL-2 in the maintenance and function of Treg cells in the adult peripheral immune system remains unclear. Here, we report that neutralization of IL-2 in mice abrogated all IL-2 receptor signaling in Treg cells, but was well tolerated and only gradually impacted Treg cell function and immune homeostasis. By contrast, despite substantially reduced IL-2 sensitivity, Treg cells maintained selective IL-2 signaling and prevented immune dysregulation following treatment with the inhibitory anti-CD25 antibody PC61. Reduction of Treg cells with a depleting version of the same CD25 antibody permitted CD8+ Teff proliferation before progressing to more widespread immune dysregulation. Thus, despite severely curtailed CD25 expression and function, Treg cells retain selective access to IL-2 that supports their anti-inflammatory functions in vivo. Antibody-mediated targeting of CD25 is being actively pursued for treatment of autoimmune disease and preventing allograft rejection, and our findings help inform therapeutic manipulation and design for optimal patient outcomes.
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影响因子：
8.8
作者：
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DOI：
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发表时间：
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