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Record W2495343707 · doi:10.1371/journal.ppat.1005805

Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection

2016· article· en· W2495343707 on OpenAlexafffund
Korey Demers, George Makedonas, Marcus Buggert, Michael A. Eller, Sarah J. Ratcliffe, Nilu Goonetilleke, Chris K. Li, Leigh Anne Eller, Kathleen Rono, Lucas Maganga, Sorachai Nitayaphan, Hannah Kibuuka, Jean-Pierre Routy, Mark K. Slifka, Barton F. Haynes, Andrew J. McMichael, Nicole F. Bernard, Merlin L. Robb, Michael R. Betts

Bibliographic record

VenuePLoS Pathogens · 2016
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsMcGill University Health Centre
FundersNational Institute of Allergy and Infectious DiseasesMedical Research CouncilCanadian Institutes of Health ResearchNational Institutes of HealthCanadian Foundation for AIDS ResearchCenter for AIDS Research, University of WashingtonUniversity of PennsylvaniaStyrelsen för Internationellt Utvecklingssamarbete
KeywordsPerforinCD8BiologyCytotoxic T cellImmunologyEffectorCytolysisT cellChronic infectionImmune systemIn vitroGenetics

Abstract

fetched live from OpenAlex

The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection.

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 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 score0.018
Threshold uncertainty score0.999

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 science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.002

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 head0.012
GPT teacher head0.228
Teacher spread0.216 · 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 teacher head, not a consensus.

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

Citations46
Published2016
Admission routes2
Has abstractyes

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