Evidence map›Paper›PMID 38470479›Full record

ArticleThe Journal of clinical investigation2024

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

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 and 7 more

Open access · goldAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Sonny R ElizaldiGraduate Group in Immunology, UCD, Davis, California, USA.
Chase E HawesGraduate Group in Immunology, UCD, Davis, California, USA.
Anil VermaDepartment of Pathology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
Yashavanth Shaan LakshmanappaCalifornia National Primate Research Center, UCD, Davis, California, USA.
Ashok R DinasarapuDepartment of Neurology, School of Medicine, Emory University, Atlanta, Georgia, USA.
Brent T SchlegelDepartment of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Dhivyaa RajasundaramDepartment of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jie LiBioinformatics Core, UCD, Davis, California, USA.
Blythe P Durbin-JohnsonBioinformatics Core, UCD, Davis, California, USA.
Zhong-Min MaCalifornia National Primate Research Center, UCD, Davis, California, USA.
Pabitra B PalDepartment of Pathology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
Danielle BeckmanCalifornia National Primate Research Center, UCD, Davis, California, USA.
Sean OttCalifornia National Primate Research Center, UCD, Davis, California, USA.
Reben RaemanDepartment of Pathology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
Jeffrey LifsonAIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, Maryland, USA.
John H MorrisonCalifornia National Primate Research Center, UCD, Davis, California, USA.
Smita S IyerDepartment of Pathology, School of Medicine, University of Pittsburgh, Pennsylvania, USA.
Oregon National Primate Research Center · USUniversity of Pittsburgh · USUniversity of California, Davis · USEmory University · USFrederick National Laboratory for Cancer Research · US

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
Targeting CD4 TFH cells to enhance HIV vaccine-induced humoral immunityK01OD023034 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI IYER, SWAMINATHAN SMITA · 2016 to 2018
$1.0M
Targeting CD4 T follicular helper cells for enhancing HIV vaccine induced humoral immunityR56AI150409 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI IYER, SWAMINATHAN SMITA · 2021 to 2021
$774k
NCI NIH HHS 75N91019D00024NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INIAID NIH HHS R56 AI150409NIH HHS K01 OD023034NIH HHS P51 OD011107
6 · The paper itself

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.

Indexed as

BrainCD4-Positive T-LymphocytesMacaca mulattaReceptors, CCR7Simian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusAnimalsImmunologic SurveillanceNeuroinflammatory DiseasesReceptors, CCR7Adaptive immunityAIDS/HIVInflammationNeurological disordersT cells

Identifiers

PMID38470479
PMCPMC11060742
OpenAlexW4394761415

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.