P16-54 LB. Blood CCR6+ Th17 and Th1Th17 but not CCR6neg Th1 cells are targets for HIV replication and their frequency is diminished in HIV-infected subjects
Bibliographic record
Abstract
Persistence of HIV in discrete CD4+ T-cell subsets is a barrier toward viral eradication. In an effort to identify primary T-cell subsets that play a critical role in HIV pathogenesis, we investigated the lineage-commitment and susceptibility to HIV infection of CD4+ T-cell subsets identified based on differential expression of the chemokine receptors CCR4, CXCR3, et CCR6. T-cell subsets were sorted from HIV-infected and -uninfected individuals by polychromatic flow cytometry. Expression of lineage-specific transcription factors and cytokines was quantified by real-time RT-PCR and ELISA, respectively. HIV replication and integration were measured by HIV-p24 ELISA and real-time PCR, respectively. The frequency of T-cell subsets was analyzed in HIV-infected and -uninfected individuals. CCR4+CXCR3negCCR6+, CCR4+CXCR3negCCR6neg, CCR4negCXCR3+CCR6+, and CCR4negCXCR3+CCR6neg T-cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. Th17 and Th1Th17 expressed the HIV co-receptors CCR5 and CXCR4 and were permissive to R5 and X4 HIV replication. Th2 expressed CXCR4 but not CCR5 and were permissive to X4 HIV only. Th1 expressed CCR5 and CXCR4, but were resistant to R5 and X4 HIV in vitro. Th17 and Th1Th17 but not Th1 cells harbored high levels of integrated HIV-DNA and their frequency was significantly diminished in HIV-infected subjects under anti-retroviral therapy. Th17 and Th1Th17 selectively produced CCL20 and expressed gut- and lymph node-homing molecules. We provide evidence that CCR6+ Th17 and Th1Th17 play a critical role in HIV pathogenesis by an increased permissiveness to HIV infection and ability to infiltrate anatomic sites of viral replication and recruit more CCR6+ T-cells to these sites. We also identified a CCR6neg Th1 subset resistant to HIV infection and depletion in vivo. New therapeutic strategies aimed at HIV eradication should interfere with HIV replication in CCR6+ Th17 and Th1Th17 subsets.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.027 | 0.007 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".