4-1BBL deficiency abrogates splenic hypotrophy observed following LCMV clone 13 infection in mice (P6130)
Bibliographic record
Abstract
Abstract Mice infected with lymphocytic choriomeningitis virus (LCMV) clone 13 develop a prolonged viral infection that is used as a model to study HIV infection in humans. The tumor necrosis factor (TNF) receptor family member 4-1BB, and its ligand, 4-1BBL, have been established as powerful modulators of anti-viral immunity. Here we reveal a novel role for 4-1BBL in splenic contraction following LCMV infection. At day 8 post-infection, WT and 4-1BBL-/- mice show spleens that are 2 times the average pre-infection weight. However, by 2 months following infection, a time point at which virus is no longer detectable in the spleen, WT spleens show splenic atrophy, contracting up to 50% below baseline, whereas 4-1BBL-/- spleens contract back to baseline size. Interestingly, although 4-1BBL-/- spleens show increased cellularity, there is a deficit in the frequency of a B220-TCRβ-CD11bintCD11cintNK1.1+ natural killer (NK) cell population. The change in spleen size and NK population is observed in 4-1BBL-/-, but not 4-1BB-/- mice, suggesting a 4-1BB-independent 4-1BBL mechanism. Using bone marrow chimeras, as well as NK depleting antibodies, work is in progress to elucidate the cell type on which 4-1BBL is required for these effects and the potential role for NK cells in controlling splenic contraction following viral infection. This study suggests a novel role for 4-1BBL in splenic contraction and could have important implications for understanding the resolution of inflammatory conditions.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".