近日，美国马克和詹妮弗·利普舒尔茨精密免疫学研究所教授Dirk Homann及其小组的研究显示，延长但有限的抗原呈递促进了“无助”记忆CD8⁺ T细胞的可逆缺陷。2025年6月25日出版的《免疫学》发表了这项成果。

使用多种宿主-病原体系统，研究团队证明无助效应CD8⁺ T细胞分化在很大程度上是正常的，具有TCF1^hi“记忆前体”的矛盾积累。然而，CD8⁺ T细胞暴露于残留抗原会损害Tmem池的发育。随着时间的推移，这些缺陷最终得以解决，记忆潜能和回忆能力得以完全恢复。他们的研究结果确定了在无助条件下延长抗原呈递是急性解决感染的短暂性CD⁸⁺ Tmem细胞功能障碍的基本决定因素，并强调了Tmem室内的可塑性，这对疫苗接种策略和其他方面都有影响。

据介绍，产生功能性记忆CD8⁺ T细胞通常需要CD4⁺ T细胞的参与。然而，在某些急性感染中，效应和记忆性CD8⁺ T （Tmem）细胞的形成似乎不受缺乏CD4⁺ T细胞帮助的影响。然而，“无助的”CD8⁺ Tmem细胞在再次挑战时可能反应不佳。无助的CD8⁺ Tmem细胞的起源和长期命运仍然不完全清楚。

附：英文原文

Title: Prolonged but finite antigen presentation promotes reversible defects of “helpless” memory CD8+ T cells

Author: Verena van der Heide, Gabriel Laghlali, Bennett Davenport, Beatrice Cubitt, Vladimir Roudko, Daniel Choo, Kevin Jhun, Etienne Humblin, Abishek Vaidya, Krista Angeliadis, Travis Dawson, Glaucia Furtado, Alice O. Kamphorst, Michael Schotsaert, Rafi Ahmed, Juan Carlos de la Torre, Dirk Homann

Issue&Volume: 2025-06-25

Abstract: Generation of functional memory CD8+ T cells typically requires engagement of CD4+ T cells. In certain acutely resolving infections, however, effector and memory CD8+ T (Tmem) cell formation appears impervious to the lack of CD4+ T cell help. Nevertheless, “helpless” CD8+ Tmem cells may respond poorly upon rechallenge. The origin and long-term fate of helpless CD8+ Tmem cells remain incompletely understood. Using multiple host-pathogen systems, we demonstrate that helpless effector CD8+ T cell differentiation was largely normal, with a paradoxical accumulation of TCF1hi “memory precursors.” However, exposure of CD8+ T cells to residual antigen impaired the development of the Tmem pool. These defects eventually resolved over time, with full restoration of memory potential and recall capacity. Our findings identify prolonged antigen presentation under helpless conditions as an essential determinant for transient CD8+ Tmem cell dysfunction in acutely resolving infections and highlight plasticity within the Tmem compartment, with implications for vaccination strategies and beyond.

DOI: 10.1016/j.immuni.2025.05.025

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00246-8