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Usage Information

Chronic SIV-Induced neuroinflammation disrupts CCR7+ CD4+ T cell immunosurveillance in the rhesus macaque brain
Sonny R. Elizaldi, … , John H. Morrison, Smita S. Iyer
Sonny R. Elizaldi, … , John H. Morrison, Smita S. Iyer
Published March 12, 2024
Citation Information: J Clin Invest. 2024;134(9):e175332. https://doi.org/10.1172/JCI175332.
View: Text | PDF
Research Article AIDS/HIV Inflammation

Chronic SIV-Induced neuroinflammation disrupts CCR7+ CD4+ T cell immunosurveillance in the rhesus macaque brain

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Abstract

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.

Authors

Sonny R. Elizaldi, Chase E. Hawes, Anil Verma, Yashavanth Shaan Lakshmanappa, Ashok R. Dinasarapu, Brent T. Schlegel, Dhivyaa Rajasundaram, Jie Li, Blythe P. Durbin-Johnson, Zhong-Min Ma, Pabitra B. Pal, Danielle Beckman, Sean Ott, Reben Raeman, Jeffrey Lifson, John H. Morrison, Smita S. Iyer

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Usage data is cumulative from June 2024 through June 2025.

Usage JCI PMC
Text version 2,521 502
PDF 380 136
Figure 845 7
Supplemental data 186 21
Citation downloads 103 0
Totals 4,035 666
Total Views 4,701

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