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Record W4405494826 · doi:10.1016/j.omtm.2024.101400

Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes

2024· article· en· W4405494826 on OpenAlexafffund
J. Ernesto Fajardo-Despaigne, Félix Lombard‐Vadnais, Adam‐Nicolas Pelletier, Ainhoa Alonso Olazabal, Sarah Pasquin, Valérie Janelle, Laurent Legault, Jean‐Sébastien Delisle, Erin E. Hillhouse, Lise Coderre, Sylvie Lesage

Bibliographic record

VenueMolecular Therapy — Methods & Clinical Development · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsMontreal Children's HospitalBioinformatics Solutions (Canada)Centre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-MontréalUniversité de MontréalHôpital Maisonneuve-Rosemont
FundersCanadian Institutes of Health ResearchFonds de Recherche du Québec - SantéDiabète Québec
KeywordsT-cell receptorType 1 diabetesCD8Characterization (materials science)Diabetes mellitusType 2 diabetesBiologyImmunologyMedicineT cellAntigenEndocrinologyMaterials scienceImmune systemNanotechnology

Abstract

fetched live from OpenAlex

CD4 − CD8 − TCRαβ + (double-negative [DN]) T cells represent a rare T cell population that promotes immunological tolerance through various cytotoxic mechanisms. In mice, autologous transfer of DN T cells has shown protective effects against autoimmune diabetes and graft-versus-host disease. Here, we characterized human DN T cells from people living with type 1 diabetes (PWT1D) and healthy controls. We found that while DN T cells and CD8 + T cells share many similarities, DN T cells are a unique T cell population, both at the transcriptomic and protein levels. We also show that by using various cytokine combinations, human DN T cells can be expanded in vitro up to 1,000-fold (mean >250-fold) and remain functional post-expansion. In addition, we report that DN T cells from PWT1D display a phenotype comparable to that of healthy controls, efficiently expand, and are highly functional. As DN T cells are immunoregulatory and can prevent T1D in various mouse models, these observations suggest that autologous DN T cells may be amenable to therapy for the prevention or treatment of T1D.

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 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 score0.340
Threshold uncertainty score0.614

Codex and Gemma teacher scores by category

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

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 head0.023
GPT teacher head0.336
Teacher spread0.312 · 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.

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

Citations1
Published2024
Admission routes2
Has abstractyes

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