Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T Cell Adaptor Gads
Bibliographic record
Abstract
Abstract Thymic development is tightly regulated by TCR signaling via the immune adaptors SLP-76 and LAT. Gads bridges the TCR-induced recruitment of SLP-76 to LAT; yet is not absolutely required for thymic progression. To better identify Gads-dependent developmental transitions, we performed tamoxifen-induced ablation of Gads (Gads iKO ), accompanied by expression of tdTomato, and compared the development of Gads-expressing (Tom − ) and - ablated (Tom + ) thymocytes within the same mouse. The frequency of Gads iKO (Tom + ) thymocytes decreased at β-selection and positive selection, confirming the Gads-dependence of these junctures; nevertheless, we observed small populations of positively-selected Gads iKO SP thymocytes. Consistent with a signaling defect, expression of CD5 was strongly impaired at the β-selection checkpoint and within the DP compartment; moreover, Gads iKO DP thymocytes exhibited reduced TCR-induced calcium flux. Surprisingly, MHC-non-responding (CD5 − ) Gads iKO DP thymocytes exhibited reduced death by neglect; instead, aberrant populations of CD5 − Gads iKO thymocytes progressed as far as the CD4 SP compartment, while lacking key characteristics of positively selected thymocytes. In an experimentally-induced model of death by neglect triggered by CD8 crosslinking, Gads was required for the preferential apoptosis of CD5 lo DP thymocytes. Our results suggest that Gads promotes passage through TCR-driven developmental checkpoints while also promoting the death by neglect of unselected 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) | 0.000 | 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".