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Efficient Enrichment of Functional ILC Subsets from Human PBMC by Immunomagnetic Selection

2018· article· en· W4313359619 on OpenAlexaff
Yanet Valdez, Stephen K. Kyei, Grace F. T. Poon, Andy I. Kokaji, Steven M. Woodside, Allen Eaves, Terry E. Thomas

Bibliographic record

VenueThe Journal of Immunology · 2018
Typearticle
Languageen
FieldImmunology and Microbiology
TopicIL-33, ST2, and ILC Pathways
Canadian institutionsTerry Fox Research InstituteBC Cancer AgencyStemcell Technologies
Fundersnot available
KeywordsCell sortingBiologyImmunomagnetic separationInterleukin-7 receptorPeripheral blood mononuclear cellImmune systemInnate lymphoid cellImmunologyFlow cytometryInnate immune systemT cellMolecular biologyIn vitroBiochemistry

Abstract

fetched live from OpenAlex

Abstract Innate lymphoid cells (ILCs) are exceedingly rare but important regulators of homeostatic and disease-associated immune processes. The frequency of ILCs in peripheral blood of healthy humans is ~0.07% of CD45+ leukocytes. ILCs lack specific cell surface markers but can be divided into distinct subsets (ILC1, 2 and 3) based on their differential expression of effector cytokines and master transcription factors. Currently, cell sorting is the most widely used method to isolate ILCs, but it is time consuming, expensive and often results in low purities and recoveries. Pre-enrichment of ILCs would allow for reduced sorting times and improved purities. Accordingly, we have developed a fast immunomagnetic negative selection method to pre-enrich all ILCs subsets from human leukapheresis samples. Briefly, unwanted cells are labelled with antibodies and magnetic particles and placed into an EasySep™ magnet. Unwanted cells are retained in the magnet and the enriched ILC fraction is simply poured off into a new tube. We find that total ILCs (defined as Lineage− CD45+ CD127+) are enriched from a frequency of 0.01 – 0.23% (n=28) to a final frequency of 17 – 86%, an enrichment of 200 – 1500 fold with virtually no loss of ILCs. ILC1 were enriched from 0.01 – 0.2% to 4.5 – 14%. ILC2 were enriched from 0.01 – 0.1% to 5.8 – 51% and ILC3 were enriched from 0.01 – 0.1% to 6 – 16%. This pre-enrichment drastically decreases sort time, allowing sorting over 3.7 × 105 ILCs from 2 × 109 PBMCs in only 12 minutes. Sorted cells maintained their functionality; when stimulated, ILC1s produced IFNγ, ILC2s secreted IL-13 and ILC3s produced IL-22. Our newly developed method of ILC pre-enrichment should aid human ILC research by enabling their rapid isolation when combined with cell sorting

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 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 score0.133
Threshold uncertainty score1.000

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 studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.010
GPT teacher head0.216
Teacher spread0.206 · 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

Citations6
Published2018
Admission routes1
Has abstractyes

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