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Record W3022122473 · doi:10.1002/eji.201948453

IL‐7 induces sCD127 release and mCD127 downregulation in human CD8 <sup>+</sup> T cells by distinct yet overlapping mechanisms, both of which are impaired in HIV infection

2020· article· en· W3022122473 on OpenAlexafffund
Sandra Côté, Stephanie C. Burke Schinkel, Tamara Berthoud, Priscila O. Barros, Maria Sanchez‐Vidales, April M. Davidson, Angela M. Crawley, Jonathan B. Angel

Bibliographic record

VenueEuropean Journal of Immunology · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsCarleton UniversityUniversity of OttawaOttawa Hospital
FundersCanadian Institutes of Health Research
KeywordsDownregulation and upregulationInterleukin-7 receptorBiologyCD8TetherinT cellCell biologyCytotoxic T cellProteasesImmunologyMolecular biologyImmune systemGeneIL-2 receptorVirusIn vitroGeneticsViral replication

Abstract

fetched live from OpenAlex

Abstract The IL‐7 receptor specific α chain, CD127, can be expressed both as a membrane‐associated (mCD127) and a soluble form (sCD127), however, the mechanisms involved in their regulation remain to be defined. We first demonstrated in primary human CD8 + T cells that IL‐7‐induced downregulation of mCD127 expression is dependent on JAK and PI3K signaling, whereas IL‐7‐induced sCD127 release is also mediated by STAT5. Following stimulation with IL‐7, expression of alternatively spliced variants of the CD127 gene, sCD127 mRNA, is reduced, but to a lesser degree than the full‐length gene. Evaluation of the role of proteases revealed that MMP‐9 was involved in sCD127 release, without affecting the expression of mCD127, suggesting it does not induce direct shedding from the cell surface. Since defects in the IL‐7/CD127 pathway occur in various diseases, including HIV, we evaluated CD8 + T cells derived from HAART‐treated HIV‐infected individuals and found that IL‐7‐induced (1) downregulation of mCD127, (2) release of sCD127, and (3) expression of the sCD127 mRNA were all impaired. Expression of mCD127 and sCD127 is, therefore, regulated by distinct, but overlapping, mechanisms and their impairment in HIV infection contributes to our understanding of the CD8 + T cell dysfunction that persists despite effective antiretroviral therapy.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.517
Threshold uncertainty score0.844

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 integrity0.0000.001
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 head0.012
GPT teacher head0.209
Teacher spread0.197 · 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

Citations9
Published2020
Admission routes2
Has abstractyes

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