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Record W3039642489 · doi:10.1002/cti2.1149

Mass cytometry reveals immune signatures associated with cytomegalovirus (CMV) control in recipients of allogeneic haemopoietic stem cell transplant and CMV‐specific T cells

2020· article· en· W3039642489 on OpenAlexaff
Helen M. McGuire, Simone Rizzetto, Barbara Withers, Leighton Clancy, Selmir Avdic, Lauren Stern, Ellis Patrick, Barbara Fazekas de St Groth, Barry Slobedman, David Gottlieb, Fabio Luciani, Emily Blyth

Bibliographic record

VenueClinical & Translational Immunology · 2020
Typearticle
Languageen
FieldMedicine
TopicCytomegalovirus and herpesvirus research
Canadian institutionsInstitute of Infection and Immunity
FundersSydney Medical SchoolMedical Research CouncilLeukaemia FoundationCancer Council NSWNational Health and Medical Research CouncilRoyal College of Pathologists of Australasia
KeywordsCytomegalovirusStem cellMass cytometryImmune systemBiologyVirologyImmunologyFlow cytometryHerpesviridaeHuman immunodeficiency virus (HIV)Viral diseaseCell biologyGeneticsPhenotype

Abstract

fetched live from OpenAlex

Abstract Objectives Cytomegalovirus (CMV) is known to have a significant impact on immune recovery post‐allogeneic haemopoietic stem cell transplant (HSCT). Adoptive therapy with donor‐derived or third‐party virus‐specific T cells (VST) can restore CMV immunity leading to clinical benefit in prevention and treatment of post‐HSCT infection. We developed a mass cytometry approach to study natural immune recovery post‐HSCT and assess the mechanisms underlying the clinical benefits observed in recipients of VST. Methods A mass cytometry panel of 38 antibodies was utilised for global immune assessment (72 canonical innate and adaptive immune subsets) in HSCT recipients undergoing natural post‐HSCT recovery ( n = 13) and HSCT recipients who received third‐party donor‐derived CMV‐VST as salvage for unresponsive CMV reactivation ( n = 8). Results Mass cytometry identified distinct immune signatures associated with CMV characterised by a predominance of innate cells (monocytes and NK) seen early and an adaptive signature with activated CD8 + T cells seen later. All CMV‐VST recipients had failed standard antiviral pharmacotherapy as a criterion for trial involvement; 5/8 had failed to develop the adaptive immune signature by study enrolment despite significant CMV antigen exposure. Of these, VST administration resulted in development of the adaptive signature in association with CMV control in three patients. Failure to respond to CMV‐VST in one patient was associated with persistent absence of the adaptive immune signature. Conclusion The clinical benefit of CMV‐VST may be mediated by the recovery of an adaptive immune signature characterised by activated 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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.741
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
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.048
GPT teacher head0.314
Teacher spread0.266 · 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 designObservational
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

Citations26
Published2020
Admission routes1
Has abstractyes

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