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Record W4393386550 · doi:10.1084/jem.20231044

Helper T cell immunity in humans with inherited CD4 deficiency

2024· article· en· W4393386550 on OpenAlexaff
Antoine Guérin, Marcela Moncada‐Vélez, Katherine Jackson, Masato Ogishi, Jérémie Rosain, Mathieu Mancini, David Langlais, Andrea C. Nunez, Samantha Webster, Jesse Goyette, Taushif Khan, Nico Marr, Danielle T. Avery, Geetha Rao, Tim Waterboer, Birgitta E. Michels, Esmeralda Neves, Cátia Iracema Morais, Jonathan London, S. Mestrallet, Pierre Quartier, Bénédicte Neven, Franck Rapaport, Yoann Seeleuthner, Atar Lev, Amos J. Simon, Jorge Montoya, Ortal Barel, Julio Gómez‐Rodríguez, Julio C. Orrego, Anne-Sophie L’Honneur, Camille Soudée, Jessica Lineth Rojas, Alejandra Vélez, Irini Sereti, Benjamin Terrier, Nancy D. Marín, Luis F. García, Laurent Abel, Stéphanie Boisson‐Dupuis, Joel Reis, António Marinho, Andrea Lisco, Emília Faria, Christopher C. Goodnow, Julia Vasconcelos, Vivien Béziat, S. Cindy, Raz Somech, Jean‐Laurent Casanova, Jacinta Bustamante, José Luis Franco, Stuart G. Tangye

Bibliographic record

VenueThe Journal of Experimental Medicine · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsMcGill UniversityMcGill Genome Centre
FundersNational Institute of Allergy and Infectious DiseasesMedical Research CouncilAgence Nationale de la RechercheFondation Bettencourt SchuellerInstitut National de la Santé et de la Recherche MédicaleInstitut National Du CancerUniversity of New South WalesHonjo International Scholarship FoundationRockefeller UniversityNational Health and Medical Research CouncilInstitut des maladies génétiques ImagineBaxaltaAmerican Association of ImmunologistsSt. Giles Foundation
KeywordsCD8BiologyImmunityImmunologyImmune systemHuman leukocyte antigenCellular immunityAntigen

Abstract

fetched live from OpenAlex

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαβ+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αβ T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.262
Teacher spread0.250 · 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 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

Citations14
Published2024
Admission routes1
Has abstractyes

Explore more

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