Temporal expression of Bim limits the development and repertoire of TCR+ double negative thymocytes and CD8αα intestinal intraepithelial lymphocytes.
Bibliographic record
Abstract
Abstract DN T cells (CD4−CD8α−TCRαβ+) and CD8αα T cells compose a major lymphocyte population in the intestine and promote gut homeostasis. Their thymic development, i.e. agonist selection, has been shown to be controlled by the pro-apoptotic factor Bim. In addition to its role in the thymus, Bim also controls peripheral T cell survival. However, the role of Bim in thymic and peripheral homeostasis of DN T and CD8αα T cells remain unclear. Here, we found that T cell-specific expression of Bim during early, but not late, thymic development limits the levels of DN T and CD8αα T cells in the spleen and iIEL compartments. The loss of Bim altered the TCR repertoire of DN T cells, but not conventional CD4 or CD8 T cells. As IL-15 controls CD8αα cell homeostasis, and antagonizes Bim in other T cells, we examined whether the additional loss of Bim would restore CD8αα T cells in IL-15−/− mice. Strikingly, the additional loss of Bim restored splenic, but not intestinal, DN T and CD8αα T cells in IL-15−/− mice. Instead, IL-15 signaling via Stat5 synergized with TCR signaling in peripheral DN T cells to increase expression of CD8α. Furthermore, adoptive transfer of splenic DN T cells gave rise to CD8αα cells in immune intact recipients. Combined, these data show that Bim functions temporally to limit the development and TCR repertoire of CD8αα precursors in the thymus. Moreover, Bim limits IL-15-driven homeostasis of CD8αα cells in the secondary lymphoid organs; but does not restrict their IL-15-driven maturation that is critical for intestinal homeostasis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".