Distinct effects of treatment with two different interferon-alpha subtypes on HIV-1-associated T-cell activation and dysfunction in humanized mice
Bibliographic record
Abstract
OBJECTIVE: Interferon-alpha (IFN-α) has been associated with excessive immune activation and dysfunction during HIV-1 infection. However, evidence suggests specific IFN-α subtypes may be beneficial rather than detrimental. This study compared the effects of treatment with two different IFN-α subtypes on indicators of T-cell activation and dysfunction during HIV-1 infection. DESIGN: Humanized mice were infected with HIV-1 for 5 weeks and then treated with two different IFN-α subtypes for an additional 3 weeks. Splenic T cells were assessed both immediately posttreatment and again 6 weeks after treatment cessation. METHODS: HIV-1 infected triple-knockout bone marrow-liver-thymus mice received daily intraperitoneal injections of either IFN-α14 or the clinically approved subtype, IFN-α2. T cells were analysed directly ex vivo for indicators of activation and dysfunction or stimulated to determine their proliferative capacity and ability to produce functional mediators. RESULTS: Unlike IFN-α2, IFN-α14 treatment reduced viremia and resulted in less activated CD4+ T cells and a lower naïve to effector CD8+ T-cell ratio. Despite exhibiting a reduced proliferative response, the frequency of CD8+ T cells from IFN-α14 treated mice that produced functional mediators and expressed markers of dysfunction was more similar to healthy controls than untreated and IFN-α2 treated mice. Frequencies of exhaustion marker expression remained higher in untreated and IFN-α2 treated mice 6 weeks posttreatment despite similar viral loads between groups at this timepoint. CONCLUSIONS: Treatment with different IFN-α subtypes had distinctive effects on T cells during HIV-1 infection. IFN-α14 was associated with fewer indicators of T-cell dysfunction whereas IFN-α2 treatment had little impact.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".