Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Sci Immunol. 2022 Feb 11;7(68):eabl6322. doi: 10.1126/sciimmunol.abl6322.
Here, we show that the capacity to manufacture IL-2 identifies constituents of the expanded CD8 T cell effector pool that display stem-like features, preferentially survive, rapidly attain memory traits, resist exhaustion, and control chronic viral challenges. The cell-intrinsic synthesis of IL-2 by CD8 T cells attenuates the ability to receive IL-2-dependent STAT5 signals, thereby limiting terminal effector formation, endowing the IL-2-producing effector subset with superior protective powers. In contrast, the non-IL-2-producing effector cells respond to IL-2 signals and gain effector traits at the expense of memory formation. Despite having distinct properties during the effector phase, IL-2-producing and nonproducing CD8 T cells appear to converge transcriptionally as memory matures to form populations with equal recall abilities. Therefore, the potential to produce IL-2 during the effector, but not memory stage, is a consequential feature that dictates the protective capabilities of the response.
在这里，我们表明制造 IL-2 的能力确定了具有干细胞样特征的扩增 CD8 T 细胞效应池的组成部分，这些细胞优先存活、迅速获得记忆特征、抵抗衰竭并控制慢性病毒挑战。CD8 T 细胞内在合成的 IL-2 减弱了接收 IL-2 依赖性 STAT5 信号的能力，从而限制了终末效应器的形成，使产生 IL-2 的效应子亚群具有更好的保护能力。相比之下，非产生 IL-2 的效应细胞响应 IL-2 信号并获得效应器特征，而牺牲了记忆形成。尽管在效应期具有不同的特性，但产生 IL-2 和不产生 IL-2 的 CD8 T 细胞似乎在记忆成熟时在转录上趋于一致，形成具有同等召回能力的群体。因此，在效应期而不是记忆期产生 IL-2 的潜力是决定反应保护能力的重要特征。
