墨尔本大学Axel Kallies课题组在研究中取得进展。他们开发出慢性感染和检查点阻断期间，淋巴结燃料KLF2依赖性效应CD8⁺ T细胞分化。这一研究成果发表在2025年9月15日出版的国际学术期刊《自然—免疫学》上。

在这里，课题组人员确定了慢性感染期间T_PEX和T_EX细胞在次要淋巴器官中的发育和功能分区化。该团队发现，干细胞样CD62L⁺ TPEX和效应样CX3CR1⁺ T_EX细胞构成了一个不同的发育谱系，由淋巴结（LN）微环境促进，依赖于转录因子KLF2。LNs作为一个生态位，迁移的树突状细胞在其中提供抗原和共刺激信号，以维持CD62L⁺ T_PEX细胞的增殖适应性和CX3CR1⁺ T_EX细胞的产生。

此外，在ICB期间，LNs完全驱动CX3CR1⁺ T_EX细胞的增殖爆发和全身传播。他们的研究发现，在全身性慢性感染和ICB治疗期间，LNs在维持T细胞分化和功能方面发挥着独特的作用。

据介绍，耗竭T（T_PEX）细胞的前体具有高度的自我更新和发育潜力，维持了耗竭CD8⁺ T（TEX）细胞反应。T_PEX细胞也在治疗性免疫检查点阻断（ICB）时驱动效应T细胞的增殖爆发。然而，调控其分化和功能的空间背景和信号尚未得到很好的定义。

附：英文原文

Title: Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade

Author: Tsui, Carlson, Heyden, Leonie, Wen, Lifen, Gago da Graa, Catarina, Potemkin, Nikita, Frolov, Aleksej, Rawlinson, Daniel, Qin, Lei, Wimmer, Verena C., Hadian-Jazi, Marjan, Malko, Darya, Su, Chun-Hsi, Li, Sining, Wilson, Kayla R., Horvatic, Helena, Wijesinghe, Sharanya K., Moreira, Marcela L., Dryburgh, Lachlan, Schienstock, Dominik, Rausch, Lisa, Utzschneider, Daniel T., Halin, Cornelia, Mueller, Scott N., Beyer, Marc D., Bedoui, Sammy, Abdullah, Zeinab, Schrder, Jan, Kallies, Axel

Issue&Volume: 2025-09-15

Abstract: Exhausted CD8+ T (TEX) cell responses are maintained by precursors of exhausted T (TPEX) cells that possess high self-renewal and developmental potential. TPEX cells also drive the proliferative burst of effector T cells upon therapeutic immune checkpoint blockade (ICB). However, the spatial context and signals that regulate their differentiation and function are not well defined. Here we identify developmental and functional compartmentalization of TPEX and TEX cells across secondary lymphoid organs during chronic infection. We show that stem-like CD62L+ TPEX and effector-like CX3CR1+ TEX cells constitute a distinct developmental lineage that is promoted by the lymph node (LN) microenvironment and dependent on the transcription factor KLF2. LNs act as a niche in which migratory dendritic cells provide antigen and costimulatory signals to maintain the proliferative fitness of CD62L+ TPEX cells and generation of CX3CR1+ TEX cells. Moreover, LNs exclusively drive the proliferative burst and systemic dissemination of CX3CR1+ TEX cells during ICB. Thus, our findings identify a unique role for LNs in the maintenance of T cell differentiation and function during systemic chronic infection and ICB therapy.

DOI: 10.1038/s41590-025-02276-7

Source: https://www.nature.com/articles/s41590-025-02276-7