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CD27 co-stimulation increases regulatory T cell survival and limits progression of atherosclerosis.

2017· article· en· W4313380564 on OpenAlexaff
Holger Winkels, Svenja Meiler, Christina Bürger, Sigrid Reim, Christian Weber, Jannie Borst, Klaus Ley, Esther Lutgens, Norbert Gerdes

Bibliographic record

VenueThe Journal of Immunology · 2017
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAtherosclerosis and Cardiovascular Diseases
Canadian institutionsInstitute of Cancer Research
Fundersnot available
KeywordsApolipoprotein EImmune systemBone marrowLesionStimulationFlow cytometryImmunologyEndocrinologyInternal medicineBiologyMedicinePathologyDisease

Abstract

fetched live from OpenAlex

Abstract Co-stimulatory signals are important shaping adaptive immunity which is pivotal to all stages of atherosclerosis. The interaction of the co-stimulatory molecules CD27 and CD70 modulates Treg development. Furthermore, T cell activation, proliferation, and also differentiation are affected by CD27-CD70 interactions. Thus, we hypothesized that the deficiency of CD27 will lead to exacerbated atherosclerosis. Cd27−/− mice were crossed with Apoe−/− mice. Cd27−/−Apoe−/− and littermate controls (Cd27+/+Apoe−/−) were sacrificed at the age of 18 and 28 weeks. Bone marrow of Cd27−/−Apoe−/− and littermate controls was transplanted into Apoe−/− recipient mice. Lesion size, histology and cellular composition were analyzed in the ascending aorta. Human and murine T cells co-localize with CD27 in atherosclerotic lesions. At early stages of atherosclerosis, Cd27−/−Apoe−/− mice displayed bigger and more complex atherosclerotic lesions. Flow cytometry revealed a significant decrease in abundance of splenic and aortic Tregs and increased apoptosis of Treg in the thymus of Cd27−/−Apoe−/− mice. In contrast, at later stages of atherosclerosis (28 weeks), splenic and lesional Treg content and atherosclerotic burden were similar. Transplantation of Cd27−/−Apoe−/− bone marrow, in contrast to control, induced increased atherosclerotic plaque size and a profound pro-inflammatory plaque phenotype accompanied by reduced frequency of aortic and splenic Tregs. Furthermore, the number of circulating leukocytes was increased. Taken together, CD27 deficiency impairs thymic Treg development which exacerbates early atherogenesis. However, the role of CD27–CD70 interactions does not affect later stages of atherosclerosis.

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 score0.003
Threshold uncertainty score0.010

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)0.0030.001

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 head0.021
GPT teacher head0.264
Teacher spread0.244 · 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".

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Citations0
Published2017
Admission routes1
Has abstractyes

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