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Record W2983661566 · doi:10.4049/jimmunol.1901072

CXCR3 Identifies Human Naive CD8+ T Cells with Enhanced Effector Differentiation Potential

2019· article· en· W2983661566 on OpenAlexaff
Gabriele De Simone, Emilia Maria Cristina Mazza, Antonino Cassotta, Alexey N. Davydov, Mirela Kuka, Veronica Zanon, Fédérica De Paoli, Eloise Scamardella, Maria Metsger, Alessandra Roberto, Karolina Pilipow, Federico Colombo, Elena Tenedini, Enrico Tagliafico, Luca Gattinoni, Domenico Mavilio, Clelia Peano, David A. Price, Satya P. Singh, Joshua Μ. Farber, Valentina Serra, Francesco Cucca, Francesco Ferrari, Valeria Orrù, Edoardo Fiorillo, Matteo Iannacone, Dmitriy M. Chudakov, Federica Sallusto, Enrico Lugli

Bibliographic record

VenueThe Journal of Immunology · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsInstitute of Infection and Immunity
FundersH2020 European Research CouncilNational Institute of Allergy and Infectious DiseasesHumanitas Research HospitalNational Science FoundationAssociazione Italiana per la Ricerca sul CancroFondazione Italiana per la Ricerca sul CancroMinistero della SaluteWellcome TrustNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungHelmut Horten StiftungInstitute for Research in BiomedicineUniversity of MinnesotaEmory UniversityGiovanni Armenise-Harvard FoundationMinistry of Science and Higher Education of the Russian Federation
KeywordsCXCR3EffectorCytotoxic T cellCell biologyBiologyImmunologyInflammationGeneticsChemokine

Abstract

fetched live from OpenAlex

Abstract In mice, the ability of naive T (TN) cells to mount an effector response correlates with TCR sensitivity for self-derived Ags, which can be quantified indirectly by measuring surface expression levels of CD5. Equivalent findings have not been reported previously in humans. We identified two discrete subsets of human CD8+ TN cells, defined by the absence or presence of the chemokine receptor CXCR3. The more abundant CXCR3+ TN cell subset displayed an effector-like transcriptional profile and expressed TCRs with physicochemical characteristics indicative of enhanced interactions with peptide–HLA class I Ags. Moreover, CXCR3+ TN cells frequently produced IL-2 and TNF in response to nonspecific activation directly ex vivo and differentiated readily into Ag-specific effector cells in vitro. Comparative analyses further revealed that human CXCR3+ TN cells were transcriptionally equivalent to murine CXCR3+ TN cells, which expressed high levels of CD5. These findings provide support for the notion that effector differentiation is shaped by heterogeneity in the preimmune repertoire of human CD8+ T cells.

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 categoriesInsufficient payload (model declined to judge)
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 score0.022
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.004
GPT teacher head0.215
Teacher spread0.210 · 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; both teacher heads agree on what is shown here.

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

Citations53
Published2019
Admission routes1
Has abstractyes

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