Defining the molecular and cellular niche for CD8 memory T cell maintenance by 4-1BB and 4-1BBL (46.18)
Bibliographic record
Abstract
Abstract Following the resolution of an infection, memory lymphocytes can persist for the lifetime of the animal and play a critical role in protection from re-infection. Using mixed BM chimeras, we show that 4-1BB on the T cells is required for maximal CD8 memory T cell response to influenza virus. 4-1BB is constitutively expressed on a fraction of CD8 memory T cells in the BM of unmanipulated mice, with much lower expression in the spleen and LN. The common gamma chain cytokines IL-2, IL-15, and IL-7 can each induce 4-1BB expression on CD8 CD44Hi cells in the absence of Ag ex vivo. However, using CD122-/- mixed BM chimeras and IL-7Ra antibody blockade, they were found to be dispensable for in vivo expression of 4-1BB on memory CD8 T cells. In contrast, the TNFR family member GITR plays a non-redundant role in inducing 4-1BB expression on CD8 memory T cells. 4-1BBL can be detected on CD11c+ cells in the spleen and BM and on CD45 negative cells in the BM. We found that 4-1BBL on radioresistant cells provides the major source of 4-1BBL to maintain the CD8 memory T cell pool detected in the BM, whereas the absence of 4-1BBL on radiosensitive cells makes an additional contribution to the CD8 memory pool detected in the spleen. This study defines a specific niche in the BM, where 4-1BB is expressed on CD8 memory T cells in a GITR-dependent manner and 4-1BBL on a radioresistant CD45 negative cell in the BM provides the source of ligand for 4-1BB-dependent memory CD8 T cell maintenance.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".