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ResearchIn-Press PreviewAIDS/HIVInflammation Open Access | 10.1172/JCI175332
1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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1Graduate Group in Immunology, University of California, Davis, Davis, United States of America
2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
3California National Primate Research Center, University of California, Davis, Davis, United States of America
4Department of Neurology, School of Medicine, Emory University, Atlanta, United States of America
5Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America
6Bioinformatics Core, University of California, Davis, Davis, United States of America
7AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, United States of America
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Published March 12, 2024 - More info
CD4 T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4 T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4 T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside CNS border tissues. Sequestering TCM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4 T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL757 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4 T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4 T cells in CNS immune surveillance and their decline during chronic SIV highlights their responsiveness to neuroinflammation.