Acquisition of residency programs by T cells entering the human brain
Summary: T cell surveillance is mandatory for maintaining central nervous system (CNS) homeostasis, while aberrant accumulation is linked to neuroinflammation. To explore the residency programs acquired by T cells through different anatomical locations of the human brain, we isolated CD8+ and CD4+ T...
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Elsevier
2025-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725007314 |
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| author | Cheng-Chih Hsiao Hendrik J. Engelenburg Jasper Rip Annet F. Wierenga-Wolf Fabiënne van Puijfelik Marvin M. van Luijn Inge Huitinga Jörg Hamann Joost Smolders |
| author_facet | Cheng-Chih Hsiao Hendrik J. Engelenburg Jasper Rip Annet F. Wierenga-Wolf Fabiënne van Puijfelik Marvin M. van Luijn Inge Huitinga Jörg Hamann Joost Smolders |
| author_sort | Cheng-Chih Hsiao |
| collection | DOAJ |
| description | Summary: T cell surveillance is mandatory for maintaining central nervous system (CNS) homeostasis, while aberrant accumulation is linked to neuroinflammation. To explore the residency programs acquired by T cells through different anatomical locations of the human brain, we isolated CD8+ and CD4+ T cells from CNS border compartments (choroid plexus and leptomeninges), intrathecal compartments (cerebrospinal fluid [CSF] and subcortical white matter [WM]), and paired peripheral blood of brain donors. Flow cytometry revealed a shared effector memory phenotype across CNS compartments that was partially induced in circulating T cells interacting with brain endothelium in vitro. Intrathecal T cells expressed full tissue-residency traits, yet T cells from WM, compared to CSF, showed reduced expression of migratory, co-stimulatory, and recent activation markers despite a similar cytokine response upon ex vivo activation. This work demonstrates the versatility of T cell phenotypes across CNS compartments and provides insight into the programs regulating their recruitment and maintenance within the CNS. |
| format | Article |
| id | doaj-art-35f6591efb1e48ee85272a50898b5617 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-35f6591efb1e48ee85272a50898b56172025-08-20T02:36:09ZengElsevierCell Reports2211-12472025-07-0144711596010.1016/j.celrep.2025.115960Acquisition of residency programs by T cells entering the human brainCheng-Chih Hsiao0Hendrik J. Engelenburg1Jasper Rip2Annet F. Wierenga-Wolf3Fabiënne van Puijfelik4Marvin M. van Luijn5Inge Huitinga6Jörg Hamann7Joost Smolders8Neuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands; Department of Experimental Immunology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, 1105 AZ Amsterdam, the Netherlands; Corresponding authorNeuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the NetherlandsDepartment of Immunology, MS Center ErasMS, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, the NetherlandsDepartment of Immunology, MS Center ErasMS, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, the NetherlandsDepartment of Immunology, MS Center ErasMS, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, the NetherlandsDepartment of Immunology, MS Center ErasMS, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, the NetherlandsNeuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands; Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, 1098 XH Amsterdam, the NetherlandsNeuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands; Department of Experimental Immunology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, 1105 AZ Amsterdam, the Netherlands; Corresponding authorNeuroimmunology Research Group, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands; Department of Immunology, MS Center ErasMS, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, the Netherlands; Department of Neurology, MS Center ErasMS, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, the Netherlands; Corresponding authorSummary: T cell surveillance is mandatory for maintaining central nervous system (CNS) homeostasis, while aberrant accumulation is linked to neuroinflammation. To explore the residency programs acquired by T cells through different anatomical locations of the human brain, we isolated CD8+ and CD4+ T cells from CNS border compartments (choroid plexus and leptomeninges), intrathecal compartments (cerebrospinal fluid [CSF] and subcortical white matter [WM]), and paired peripheral blood of brain donors. Flow cytometry revealed a shared effector memory phenotype across CNS compartments that was partially induced in circulating T cells interacting with brain endothelium in vitro. Intrathecal T cells expressed full tissue-residency traits, yet T cells from WM, compared to CSF, showed reduced expression of migratory, co-stimulatory, and recent activation markers despite a similar cytokine response upon ex vivo activation. This work demonstrates the versatility of T cell phenotypes across CNS compartments and provides insight into the programs regulating their recruitment and maintenance within the CNS.http://www.sciencedirect.com/science/article/pii/S2211124725007314CP: NeuroscienceCP: Immunology |
| spellingShingle | Cheng-Chih Hsiao Hendrik J. Engelenburg Jasper Rip Annet F. Wierenga-Wolf Fabiënne van Puijfelik Marvin M. van Luijn Inge Huitinga Jörg Hamann Joost Smolders Acquisition of residency programs by T cells entering the human brain Cell Reports CP: Neuroscience CP: Immunology |
| title | Acquisition of residency programs by T cells entering the human brain |
| title_full | Acquisition of residency programs by T cells entering the human brain |
| title_fullStr | Acquisition of residency programs by T cells entering the human brain |
| title_full_unstemmed | Acquisition of residency programs by T cells entering the human brain |
| title_short | Acquisition of residency programs by T cells entering the human brain |
| title_sort | acquisition of residency programs by t cells entering the human brain |
| topic | CP: Neuroscience CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725007314 |
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