Priming of CD8 T cells in established chronic viral infection directs a distinct differentiation and functional program for long-term immunity
Bibliographic record
Abstract
Abstract CD8 T cell exhaustion impedes control of chronic virus infection, yet how CD8 T cell fate decisions and function are instilled and progressively controlled throughout infection is unclear. We demonstrate that in contrast to T cells primed at the onset of persistent viral infection, CD8 T cells primed after the chronic infection is established preferentially generate into memory-like cells that resist contraction, are less exhausted and have heightened responsiveness to immunotherapy. Mechanistically, viral persistence down-regulates APC activation machinery, decreasing T cell intrinsic TCR and CD28 signaling upon priming. The lower signal intensity provides the required threshold for activation and proliferation, but alters transcriptional programming and cellular differentiation to enable long-term retention of antiviral functions despite high levels of virus replication. In the absence of strong antigenic signaling, IL-21 acquires the ability to induce functional effectors, while preserving the memory-like reservoir. Analogous mechanisms also govern differentiation of anti-tumor CD8 T cells in the tumor microenvironment during chronic viral infection, undermining tumor control. Thus, dynamic changes in signal intensity and IL-21 usage during chronic infection function as fate-assigning rheostats to resist exhaustion and program long-term immunity.
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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) | 0.000 | 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) | 0.002 | 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".