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Record W2913946693 · doi:10.1038/s41467-019-08798-7

PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals

2019· article· en· W2913946693 on OpenAlexafffund
Rémi Fromentin, Sandrina DaFonseca, Cecilia T. Costiniuk, Mohamed El‐Far, Francesco A. Procopio, Frederick Hecht, Rebecca Hoh, Steven G. Deeks, Daria J. Hazuda, Sharon R. Lewin, Jean‐Pierre Routy, Rafick‐Pierre Sékaly, Nicolas Chomont

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversité de MontréalMcGill University Health CentreCaprion (Canada)Centre Hospitalier de l’Université de Montréal
FundersCanadian Institutes of Health ResearchUniversity of California, San FranciscoNational Institutes of HealthMcGill UniversityCanadian Foundation for AIDS ResearchNational Institute of Allergy and Infectious DiseasesNational Health and Medical Research CouncilDelaney AIDS Research EnterpriseStyrelsen för Internationellt UtvecklingssamarbeteMedical Research CouncilamfAR, The Foundation for AIDS Research
KeywordsBlockadeMonoclonal antibodyEx vivoCytotoxic T cellImmune systemLatency (audio)ImmunologyT-cell receptorT cellBiologyVirologyImmune checkpointAntibodyPembrolizumabJurkat cellsImmunotherapyCancer researchMedicineIn vivoReceptorIn vitro

Abstract

fetched live from OpenAlex

Abstract HIV persists in latently infected CD4 + T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4 + T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.587
Threshold uncertainty score0.998

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.012

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.264
Teacher spread0.254 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; both teacher heads agree on what is shown here.

Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations215
Published2019
Admission routes2
Has abstractyes

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