Antigen-driven activation of CD8⁺ T cells results in the development of a robust anti-pathogen response and ultimately leads to the establishment of long-lived memory T cells. During the primary response, CD8⁺ T cells interact multiple times with cognate antigen on distinct types of antigen-presenting cells. The timing, location and context of these antigen encounters significantly impact the differentiation programs initiated in the cells. Moderate re-activation in the periphery promotes the establishment of the tissue-resident memory T cells that serve as sentinels at the portal of pathogen entry. Under some circumstances, moderate re-activation of T cells in the periphery can result in the excessive expansion and accumulation of circulatory memory T cells, a process called memory inflation. In contrast, excessive re-activation stimuli generally impede conventional T-cell differentiation programs and can result in T-cell exhaustion. However, these conditions can also elicit a small population of exhausted T cells with a memory-like signature and self-renewal capability that are capable of responding to immunotherapy, and restoration of functional activity. Although it is clear that antigen re-encounter during the primary immune response has a significant impact on memory T-cell development, we still do not understand the molecular details that drive these fate decisions. Here, we review our understanding of how antigen encounters and re-activation events impact the array of memory CD8⁺ T-cell subsets subsequently generated. Identification of the molecular programs that drive memory T-cell generation will advance the development of new vaccine strategies that elicit high-quality CD8⁺ T-cell memory.

中文翻译：

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同源抗原多次命中对记忆 CD8+ T 细胞命运的影响。

CD8 ⁺ T 细胞的抗原驱动激活导致强大的抗病原体反应的发展，并最终导致长寿命记忆 T 细胞的建立。在初级反应期间，CD8 ⁺T 细胞与不同类型的抗原呈递细胞上的同源抗原相互作用多次。这些抗原相遇的时间、位置和背景会显着影响细胞中启动的分化程序。外周的中度再激活促进了组织驻留记忆 T 细胞的建立，这些 T 细胞充当病原体进入门户的哨兵。在某些情况下，外周T细胞的适度重新激活会导致循环记忆T细胞过度扩张和积累，这一过程称为记忆膨胀。相比之下，过度的再激活刺激通常会阻碍传统的 T 细胞分化程序，并可能导致 T 细胞衰竭。然而，这些条件还可以引发一小群疲惫的 T 细胞，这些 T 细胞具有类似记忆的特征和自我更新能力，能够对免疫疗法做出反应并恢复功能活动。虽然很明显，在初级免疫反应期间抗原的重新接触对记忆 T 细胞的发育有重大影响，但我们仍然不了解驱动这些命运决定的分子细节。在这里，我们回顾了我们对抗原相遇和重新激活事件如何影响记忆 CD8 阵列的理解 我们仍然不了解驱动这些命运决定的分子细节。在这里，我们回顾了我们对抗原相遇和重新激活事件如何影响记忆 CD8 阵列的理解 我们仍然不了解驱动这些命运决定的分子细节。在这里，我们回顾了我们对抗原相遇和重新激活事件如何影响记忆 CD8 阵列的理解⁺随后产生的 T 细胞亚群。确定驱动记忆 T 细胞生成的分子程序将推动新疫苗策略的开发，从而引发高质量的 CD8 ⁺ T 细胞记忆。