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Chimeric antigen receptors on Regulatory T cells as a treatment strategy in autoimmune diseases

2022· article· en· W4313404855 on OpenAlexaffabout
Harika Dasari

Bibliographic record

VenueThe Journal of Immunology · 2022
Typearticle
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsChimeric antigen receptorImmunologyFlow cytometryCD28Regulatory T cellT cellFOXP3BiologyCancer researchIL-2 receptorImmune system

Abstract

fetched live from OpenAlex

Abstract Research question Can CAR-MOG Tregs help curb the neuroinflammation in a MS mouse model? Objectives Methods To test this out, we sorted Tregs from human peripheral blood or murine spleens using T cell enrichment followed by flow-cytometric sorting and amplified using Dynabeads (human CD3/CD28 activator) for Tregs proliferation and stained for Treg markers to ascertain the purity of isolated Tregs. We then constructed a second-generation CAR against MOG monoclonal antibody (8.18 C5) and transduce Tregs and Tconvs to test the transduction efficacy and suppressive function of CAR-Tregs. To test the killing function of CAR-MOG-Tconv and compared this to that of CAR MOG Tregs, we set up a cytotoxicity assay against a cell line modified to express MOG. Additionally we performed suppression assays with control Tregs and CAR transduced Tregs to determine if CAR transduction affects the immunosuppressive capacity of Tregs. Results CAR Tconv and CAR Tregs show specificity against K562 cell line modified to express MOG, CAR Tregs have a lower killing capacity compared to CAR Tconv. CAR Tregs do not lose their immunosuppressive function and are comparable to the untransduced Tregs. CAR Tregs upon co-culture with Target cell line (K562 MOG) express activation markers and increased expression of cytokines such as IL-10, and TGF beta. Supported by Canada Graduate Scholarships Doctoral Award (CGS D)

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: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

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 integrity0.0000.001
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 head0.011
GPT teacher head0.226
Teacher spread0.215 · 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 designTheoretical or conceptual
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
Published2022
Admission routes2
Has abstractyes

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