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Record W3200587016 · doi:10.26508/lsa.202101081

Elevated glycolysis imparts functional ability to CD8<sup>+</sup> T cells in HIV infection

2021· article· en· W3200587016 on OpenAlexafffund
AKM Nur-ur Rahman, Jun Liu, Shariq Mujib, Segen Kidane, Arman Ali, Steven Szep, Carrie Han, Phil Bonner, Michael Parsons, Erika Benko, Colin Kovacs, Feng Yun Yue, Mario Ostrowski

Bibliographic record

VenueLife Science Alliance · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsSt. Michael's HospitalMaple Leaf Medical ClinicLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalUniversity of Toronto
FundersScheme for Promotion of Academic and Research CollaborationCanadian Institutes of Health ResearchHospital for Sick ChildrenOntario HIV Treatment Network
KeywordsGlycolysisHuman immunodeficiency virus (HIV)CD8VirologyBiologyImmunologyChemistryMetabolismBiochemistryImmune system

Abstract

fetched live from OpenAlex

The mechanisms inducing exhaustion of HIV-specific CD8 + T cells are not fully understood. Metabolic programming directly influences T-cell differentiation, effector function, and memory. We evaluated metabolic profiles of ex vivo CD8 + T cells in HIV-infected individuals. The baseline oxygen consumption rate of CD8 + T cells was elevated in all infected individuals and CD8 + T cells were working at maximal respiratory capacity. The baseline glycolysis rate was enhanced only during early untreated HIV and in viral controllers, but glycolytic capacity was conserved at all stages of infection. CD8 + T-cell mTOR activity was found to be reduced. Enhanced glycolysis was crucial for HIV-specific killing of CD8 + T cells. CD8 + T-cell cytoplasmic GAPDH content was reduced in HIV, but less in early infection and viral controllers. Thus, CD8 + T-cell exhaustion in HIV is characterized by reduced glycolytic activity, enhanced OXPHOS demands, dysregulated mTOR, and reduced cytoplasmic GAPDH. These data provide potential metabolic strategies to reverse CD8 + T-cell dysfunction in HIV.

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)0.001
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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.361
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.007

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 head0.021
GPT teacher head0.277
Teacher spread0.256 · 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 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

Citations27
Published2021
Admission routes2
Has abstractyes

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