Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals
Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals
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DOI：
10.4049/jimmunol.1800906
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发表时间：
2018-12-15
影响因子：
4.4
通讯作者：
Kalia, Vandana
中科院分区：
文献类型：
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作者：
Sarkar, Surojit;Yuzefpolskiy, Yevgeniy;Kalia, Vandana
IL-1通常被认为是适应性免疫应答的放大器，已经提出在用弱免疫原免疫期间用作佐剂。然而，它对记忆T细胞功能的影响在很大程度上仍然不确定。使用小鼠急性病毒感染模型，在本文中，我们表明，除了增加Ag特异性池的大小，IL-1信号直接作用于CD 8 T细胞，以促进效应和记忆反应的质量。T细胞中IL-1 R1或MyD 88信号传导的消融导致功能损害;每个细胞产生多种细胞因子的能力（多功能性）和响应抗原再刺激的回忆增殖的潜力都受到损害。在引发过程中补充IL-1增强了Ag特异性CD 8 T细胞通过MyD 88-IRAK 1/4轴的扩增，从而产生了能够响应于再激发而进行稳健的二次扩增的更大的记忆池。总之，这些发现证明了IL-1-MyD 88轴在编程记忆CD 8 T细胞应答的数量和质量中的关键作用，并支持了IL-1补充剂可用于增强针对癌症和慢性感染的过继性T细胞疗法的观点。
IL-1, generally considered an amplifier of adaptive immune responses, has been proposed for use as adjuvant during immunization with weak immunogens. However, its effects on memory T cell function remain largely undefined. Using the murine model of acute viral infection, in this paper, we show that in addition to augmenting the size of the Ag-specific pool, IL-1 signals act directly on CD8 T cells to promote the quality of effector and memory responses. Ablation of IL-1R1 or MyD88 signaling in T cells led to functional impairment; both the ability to produce multiple cytokines on a per cell basis (polyfunctionality) and the potential for recall proliferation in response to antigenic restimulation were compromised. IL-1 supplementation during priming augmented the expansion of Ag-specific CD8 T cells through the MyD88-IRAK1/4 axis, resulting in a larger memory pool capable of robust secondary expansion in response to rechallange. Together, these findings demonstrate a critical role of the IL-1-MyD88 axis in programming the quantity and quality of memory CD8 T cell responses and support the notion that IL-1 supplementation may be exploited to enhance adoptive T cell therapies against cancers and chronic infections.