Home > Publications Database > Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade. > print

001     281515
005     20251102002052.0
024 7 _ |a 10.1038/s41590-025-02276-7
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024 7 _ |a 1529-2908
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024 7 _ |a 1529-2916
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037 _ _ |a DZNE-2025-01134
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Tsui, Carlson
|0 0000-0003-0642-814X
|b 0
245 _ _ |a Lymph nodes fuel KLF2-dependent effector CD8+ T cell differentiation during chronic infection and checkpoint blockade.
260 _ _ |a London
|c 2025
|b Springer Nature Limited
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
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650 _ 7 |a Kruppel-Like Transcription Factors
|2 NLM Chemicals
650 _ 7 |a Klf2 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Immune Checkpoint Inhibitors
|2 NLM Chemicals
650 _ 7 |a CX3C Chemokine Receptor 1
|2 NLM Chemicals
650 _ 7 |a Cx3cr1 protein, mouse
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Lymph Nodes: immunology
|2 MeSH
650 _ 2 |a Cell Differentiation: immunology
|2 MeSH
650 _ 2 |a CD8-Positive T-Lymphocytes: immunology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Kruppel-Like Transcription Factors: metabolism
|2 MeSH
650 _ 2 |a Kruppel-Like Transcription Factors: genetics
|2 MeSH
650 _ 2 |a Kruppel-Like Transcription Factors: immunology
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Immune Checkpoint Inhibitors: pharmacology
|2 MeSH
650 _ 2 |a CX3C Chemokine Receptor 1: metabolism
|2 MeSH
650 _ 2 |a Lymphocytic Choriomeningitis: immunology
|2 MeSH
650 _ 2 |a Lymphocytic choriomeningitis virus: immunology
|2 MeSH
650 _ 2 |a Persistent Infection: immunology
|2 MeSH
650 _ 2 |a Dendritic Cells: immunology
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Lymphocyte Activation: immunology
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
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700 1 _ |a Heyden, Leonie
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700 1 _ |a Wen, Lifen
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700 1 _ |a Gago da Graça, Catarina
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700 1 _ |a Potemkin, Nikita
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700 1 _ |a Frolov, Aleksej
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700 1 _ |a Rawlinson, Daniel
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700 1 _ |a Qin, Lei
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700 1 _ |a Wimmer, Verena C
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700 1 _ |a Hadian-Jazi, Marjan
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700 1 _ |a Malko, Darya
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700 1 _ |a Su, Chun-Hsi
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700 1 _ |a Li, Sining
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700 1 _ |a Wilson, Kayla R
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700 1 _ |a Horvatic, Helena
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700 1 _ |a Wijesinghe, Sharanya K
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700 1 _ |a Moreira, Marcela L
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700 1 _ |a Dryburgh, Lachlan
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700 1 _ |a Schienstock, Dominik
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700 1 _ |a Rausch, Lisa
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700 1 _ |a Utzschneider, Daniel T
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700 1 _ |a Halin, Cornelia
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700 1 _ |a Mueller, Scott N
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700 1 _ |a Beyer, Marc D
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700 1 _ |a Bedoui, Sammy
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700 1 _ |a Abdullah, Zeinab
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700 1 _ |a Schröder, Jan
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700 1 _ |a Kallies, Axel
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773 _ _ |a 10.1038/s41590-025-02276-7
|g Vol. 26, no. 10, p. 1752 - 1765
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