4‐1BBL is a critical component in the costimulation dependent rescue of functionally impaired HIV‐specific CTL
Bibliographic record
Abstract
During chronic infection, HIV‐specific CD8 T cells exhibit progressive signs of functional impairment, attributed to persistent antigenic stimulation, up‐regulation of the inhibitory receptor PD‐1, and declining T cell help. Strategies that directly improve CD8 T cell function offer the potential of restoring immune control of HIV. Although PD‐1 expression has been identified as a cause of functional impairment in HIV, in this study, PD‐1 expression was observed on only a subfraction of HIV‐specific CTL in a subfraction of donors, whereas HIV‐specific CTL from all donors exhibited a limited repertoire of effector functions. 4‐1BBL is emerging as an important stimulator of antiviral CD8 T cell responses. Regardless of the PD‐1 status of the donors, here we show that 4‐1BBL, when combined with CD80 or CD70, expands a population of Ag‐specific CD8 T cells expressing multiple markers of effector function, from the functionally impaired starting population. In contrast, CD70 in combination with CD80 was insufficient for these effects and the related TNF family ligand, LIGHT, had negligible activity. The unique contribution of 4‐1BBL correlated with down‐regulation of the proapoptotic molecule Bim in activated CD8 T cells. Decreasing the level of TRAF1 in T cells using siRNA resulted in increased levels of Bim in the 4‐1BBL‐stimulated CD8s. Thus, costimulation via 4‐1BBL leads to TRAF1‐dependent Bim down‐modulation in T cells, resulting in increased T cell expansion. These studies identify 4‐1BBL as a critical component in therapeutic strategies aimed at improving CD8 T cell function.
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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) | 0.001 | 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) | 0.001 | 0.001 |
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".