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Record W4416449461 · doi:10.1093/jimmun/vkaf283.1848

Investigating the effect of invariant natural killer T cell receptor on T cell development and function from human pluripotent stem cells 4127

2025· article· en· W4416449461 on OpenAlexaff
Charles Lau, Karina Akhmedova, Thristan P. Taberna, Ross D. Jones, Frank P. K. Hsu, Carla Zimmerman, Yale S. Michaels, Peter W. Zandstra

Bibliographic record

VenueThe Journal of Immunology · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsUniversity of ManitobaUniversity of British Columbia
Fundersnot available
KeywordsNatural killer T cellT cellInduced pluripotent stem cellStem cellImmune systemCytotoxic T cellCellular differentiationTranscription factorAntigen

Abstract

fetched live from OpenAlex

Abstract Description Invariant Natural Killer T (iNKT) cells are a subset of unconventional T cells that recognize lipid antigens independent of HLA molecules. This ability to bypass donor-recipient matching, along with their rapid cytokine production, makes them an attractive immunotherapy agent. However, their low frequency in vivo makes investigating their functions difficult. Efforts have been made to scale up “iNKT-like” cell production by manipulating iNKT T cell receptor (iTCR) expression in stem cells. However, their use of xenogeneic feeder cells and non-chemically defined systems make understanding their developmental niche and clinical translation difficult. To investigate if iTCR expression during T cell development affects its developmental trajectory, we turn to combine our lab’s expertise in niche and genetic engineering. Using our feeder-free and chemically defined differentiation protocol, we can robustly generate mature conventional T cells from human pluripotent stem cells (hPSCs). By integrating a functional iTCR into hPSCs through CRISPR/Cas gene editing, we generated different subsets of iTCR expressing mature T cells that express the innate transcription factor PLZF. Further comparison with other engineered hPSC-derived T cells will help elucidate how iTCR expression and signaling regulate iNKT cell development. Ultimately, we aim to harness specific properties of unconventional T cells to develop more effective off-the-shelf T cell therapeutics for various diseases. Topic Categories Hematopoiesis and Immune System Development (HEM)

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 score0.002
Threshold uncertainty score0.006

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.008
GPT teacher head0.206
Teacher spread0.198 · 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

Citations0
Published2025
Admission routes1
Has abstractyes

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