Chronic virus infection drives CD8 T cell-mediated thymic destruction and impaired negative selection
Bibliographic record
Abstract
Chronic infection provokes alterations in inflammatory and suppressive pathways that potentially affect the function and integrity of multiple tissues, impacting both ongoing immune control and restorative immune therapies. Here we demonstrate that chronic lymphocytic choriomeningitis virus infection rapidly triggers severe thymic depletion, mediated by CD8 T cell-intrinsic type I interferon (IFN) and signal transducer and activator of transcription 2 (Stat2) signaling. Occurring temporal to T cell exhaustion, thymic cellularity reconstituted despite ongoing viral replication, with a rapid secondary thymic depletion following immune restoration by anti-programmed death-ligand 1 (PDL1) blockade. Therapeutic hematopoietic stem cell transplant (HSCT) during chronic infection generated new antiviral CD8 T cells, despite sustained virus replication in the thymus, indicating an impairment in negative selection. Consequently, low amounts of high-affinity self-reactive T cells also escaped the thymus following HSCT during chronic infection. Thus, by altering the stringency and partially impairing negative selection, the host generates new virus-specific T cells to replenish the fight against the chronic infection, but also has the potentially dangerous effect of enabling the escape of self-reactive T cells.
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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) | 0.001 | 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 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".