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Record W2945581457 · doi:10.1111/aji.13143

Characterization of CD4<sup>+</sup> T cell subsets and HIV susceptibility in the inner and outer foreskin of Ugandan men

2019· article· en· W2945581457 on OpenAlexaff
Ronald M. Galiwango, Sergey Yegorov, Vineet Joag, Jessica L. Prodger, Kamnoosh Shahabi, Sanja Huibner, Enoch Muyanja, Brian Roy Kabuubi, Annmarie Namuniina, Annet Nalutaaya, Aloysius Ssemaganda, Fredrick Lutwama, Paul Kato Kitandwe, Annet Nanvubya, Juliet Mpendo, Bernard S. Bagaya, Noah Kiwanuka, Rupert Kaul

Bibliographic record

VenueAmerican Journal of Reproductive Immunology · 2019
Typearticle
Languageen
FieldMedicine
TopicGenital Health and Disease
Canadian institutionsUniversity Health NetworkUniversity of Toronto
Fundersnot available
KeywordsForeskinProinflammatory cytokineImmunologyImmune systemCytokineT cellBiologyMolecular biologyMedicineInflammationCell cultureGenetics

Abstract

fetched live from OpenAlex

Abstract Problem Biological mechanisms of foreskin HIV acquisition are poorly defined. The inner foreskin is preferentially infected in explant models, so we hypothesized that this site would be enriched for HIV‐susceptible CD4 + T cells and proinflammatory/chemoattractant cytokines. Method of study A total of 42 HIV‐uninfected Ugandan men without genital symptoms provided foreskin tissues and swabs at the time of elective penile circumcision. The immune phenotype of foreskin‐derived CD4 + T cells and entry of a CCR5‐tropic HIV pseudovirus was characterized, and specific cytokine levels assayed by multiplexed chemiluminescent ELISA. Results Unexpectedly, outer foreskin CD4 + T cells more frequently expressed CCR5 (median 29.2% vs 22.9%, P = 0.01) and CD69 (median 36.5% vs 15%, P &lt; 0.01), and on a per‐cell basis, HIV entry was higher. However, overall CD4 + T cell density was approximately twofold higher in the inner foreskin, and several highly susceptible T cell subsets were increased at this site, including Th17 cells (20.0% vs 14.1%, P = 0.0021). Specific pro‐inflammatory cytokine levels were also higher on the inner foreskin surface (IL‐17, IL‐8, RANTES and IL‐1β; all P &lt; 0.05). Conclusion There was marked heterogeneity in CD4 + T cell populations and immune milieu between inner and outer foreskin tissues. Despite higher per‐cell viral entry into CD4 + T cells from the outer foreskin, the higher target cell density and enriched pro‐inflammatory cytokines of the inner foreskin suggest that this may be a preferential site for HIV acquisition.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.165
Threshold uncertainty score0.255

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.006
GPT teacher head0.245
Teacher spread0.239 · 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.

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

Citations13
Published2019
Admission routes1
Has abstractyes

Explore more

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