Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T‐Cell Adaptor Gads
Bibliographic record
Abstract
ABSTRACT Thymocyte β‐selection and positive‐selection depend on TCR signaling via the immune adaptors SLP‐76 and LAT. Gads bridges the recruitment of SLP‐76 to LAT, yet is not required for the maturation of single positive (SP) thymocytes. To illuminate this paradox, we performed tamoxifen‐induced ablation of Gads (Gads iKO ), accompanied by the expression of tdTomato, and compared the development of Gads‐expressing (Tom − ) and Gads‐ablated (Tom + ) thymocytes within the same mouse. Gads iKO (Tom + ) thymocytes exhibited impaired β‐ and positive‐selection, yet δ‐selection was not affected. While susceptible to apoptosis ex vivo, the marked accumulation of self‐MHC nonresponding (CD5 − ) Gads iKO DP thymocytes suggested the possibility of impaired death by neglect in situ. Further supporting this notion, Gads iKO CD5 lo DP thymocytes exhibited reduced apoptosis in situ and reduced CD8‐induced apoptosis ex vivo. Most Gads iKO CD4 SP thymocytes were positively selected, yet a distinct population of unselected (CD5 − TCRβ neg/low CCR7 lo CD24 hi ) CD4 SP thymocytes was seen only in the absence of Gads. This unselected population did not include Treg or TCRγδ subsets; rather, it encompassed CD44 lo CD25 + cells, resembling pre‐β‐selection thymocytes. Our results suggest that Gads promotes passage through key TCR‐driven developmental checkpoints while repressing the progression of unselected DN and DP thymocytes.
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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 | 0.000 |
| 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".