CD137 signals program the TCR⍺β+ CD8⍺⍺ intraepithelial lymphocyte population for survival 2139
Bibliographic record
Abstract
Abstract Description A population of TCRαβ+ CD8αα Intraepithelial Lymphocytes (IEL) reside in the intestine and perform regulatory roles. While most developing αβ T cells that experience agonist signals in the thymus are deleted as a central tolerance mechanism, thymic precursors of TCRαβ+ CD8αα IEL (IELp) require agonist TCR signals for selection, however, other signals that promote the generation of this unique intestinal T cell population are not fully understood. To gain insight into gene expression differences that underly IELp selection, we completed a trajectory analysis of thymic IELp using scRNA-seq and flow cytometry. We identified CD137, a costimulatory receptor in the TNF receptor superfamily, as a candidate for contributing to IELp maturation. CD137 was expressed on both thymocytes with a gene expression profile characterizing clonal deletion and IELp selection. CD137 was upregulated during thymic IELp development and maintained in the periphery on the most highly self-reactive IELp. Analysis of CD137-deficient mice and competitive mixed bone marrow chimeras supported a role for CD137 in generating CD8αα IEL but not thymic IELp maturation, nor in upregulating of trafficking molecules needed to enter the intestinal epithelium. However, in vitro culture with IL-15 suggested a survival defect in CD137-deficient IEL. Taken together, our data suggest that the most highly TCR signaled IELp receive CD137 signals that program them for long-term survival as intestinal residents. Funding Sources Supported by a CIHR Project Grant. Topic Categories Hematopoiesis and Immune System Development (HEM)
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) | 0.006 | 0.002 |
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".