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Record W4292111508 · doi:10.1016/j.cmet.2022.07.012

Carbon source availability drives nutrient utilization in CD8+ T cells

2022· article· en· W4292111508 on OpenAlexfundno aff
Irem Kaymak, Katarzyna M. Luda, Lauren R. Duimstra, H. Eric, Joseph Longo, Michael S. Dahabieh, Brandon Faubert, Brandon M. Oswald, McLane J. Watson, Susan M. Kitchen-Goosen, Lisa M. DeCamp, Shelby E. Compton, Zhen Fu, Ralph J. DeBerardinis, Kelsey S. Williams, Ryan D. Sheldon, Russell G. Jones

Bibliographic record

VenueCell Metabolism · 2022
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsnot available
FundersDivision of Cancer Epidemiology and Genetics, National Cancer InstituteNational Cancer InstitutePaul G. Allen Frontiers GroupNational Institute of Allergy and Infectious DiseasesDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesFonds de Recherche du Québec - SantéVan Andel Research InstituteDivision of Cancer Prevention, National Cancer InstituteHoward Hughes Medical Institute
KeywordsBiologyCitric acid cycleCell biologyEffectorCD8Carbohydrate metabolismMetabolismBiochemistryImmunologyImmune system

Abstract

fetched live from OpenAlex

How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in cell culture medium broadly impacts glucose utilization by CD8 + T cells, independent of transcriptional changes in metabolic reprogramming. The presence of PCSs reduced glucose contribution to the TCA cycle and increased effector function of CD8 + T cells, with lactate directly fueling the TCA cycle. In fact, CD8 + T cells responding to Listeria infection preferentially consumed lactate over glucose as a TCA cycle substrate in vitro , with lactate enhancing T cell bioenergetic and biosynthetic capacity. Inhibiting lactate-dependent metabolism in CD8 + T cells by silencing lactate dehydrogenase A (Ldha) impaired both T cell metabolic homeostasis and proliferative expansion in vivo . Together, our data indicate that carbon source availability shapes T cell glucose metabolism and identifies lactate as a bioenergetic and biosynthetic fuel for CD8 + effector T cells.

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 score0.003
Threshold uncertainty score0.010

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)0.0030.001

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 head0.013
GPT teacher head0.218
Teacher spread0.205 · 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

Citations159
Published2022
Admission routes1
Has abstractno

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