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Record W4301394762 · doi:10.1016/j.xcrm.2022.100766

Memory CD4+ T cells that co-express PD1 and CTLA4 have reduced response to activating stimuli facilitating HIV latency

2022· article· en· W4301394762 on OpenAlexaff
Thomas A. Rasmussen, Jennifer M. Zerbato, Ajantha Rhodes, Carolin Tumpach, Ashanti Dantanarayana, James McMahon, Jillian S. Y. Lau, Judy Chang, Céline Gubser, Wendy J. Brown, Rebecca Hoh, Melissa Krone, Rachel D. Pascoe, Chris Chiu, Michael Bramhall, Hyun Jae Lee, Ashraful Haque, Rémi Fromentin, Nicolas Chomont, Jeffrey M. Milush, Renée M. van der Sluis, Sarah Palmer, Steven G. Deeks, Paul Cameron, Vanessa A. Evans, Sharon R. Lewin

Bibliographic record

VenueCell Reports Medicine · 2022
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsCentre Hospitalier de l’Université de Montréal
FundersNational Institute of Allergy and Infectious DiseasesNational Institute of Mental HealthNational Health and Medical Research CouncilNovo Nordisk FondenDelaney AIDS Research EnterpriseForskerakademietGilead SciencesAbbVieamfAR, The Foundation for AIDS ResearchMerckNational Institutes of HealthAmerican Foundation for Aging ResearchEli Lilly and CompanyBristol-Myers Squibb
KeywordsCytotoxic T cellDownregulation and upregulationCell sortingT cellTIGITBiologyCD8ImmunologyCell biologyCancer researchFlow cytometryImmune systemGene

Abstract

fetched live from OpenAlex

Programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) suppress CD4 + T cell activation and may promote latent HIV infection. By performing leukapheresis (n = 21) and lymph node biopsies (n = 8) in people with HIV on antiretroviral therapy (ART) and sorting memory CD4 + T cells into subsets based on PD1/CTLA4 expression, we investigate the role of PD1 and CTLA 4 in HIV persistence. We show that double-positive (PD1 + CTLA4 + ) cells in blood contain more HIV DNA compared with double-negative (PD1 − CTLA4 − ) cells but still have a lower proportion of cells producing multiply spliced HIV RNA after stimulation as well as reduced upregulation of T cell activation and proliferation markers. Transcriptomics analyses identify differential expression of key genes regulating T cell activation and proliferation with MAF, KLRB1, and TIGIT being upregulated in double-positive compared with double-negative cells, whereas FOS is downregulated. We conclude that, in addition to being enriched for HIV DNA, double-positive cells are characterized by negative signaling and a reduced capacity to respond to stimulation, favoring HIV latency.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0050.001

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 head0.030
GPT teacher head0.297
Teacher spread0.267 · 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations38
Published2022
Admission routes1
Has abstractyes

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