Impaired T cell function and CD8 memory maintenance in a novel IL-7Rα knock-in mouse (B30)
Bibliographic record
Abstract
Abstract Interleukin (IL)-7 is an essential growth factor for thymocyte development and survival of peripheral T cells, specifically CD8+ memory T cells. Current models such as IL-7 or IL-7 receptor alpha (IL-7Rα) knock-out mice have demonstrated the necessity of IL-7 signaling in these processes, but are unable to delineate the involvement of downstream pathways. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Rα Y449XXM motif in mice by knock-in mutagenesis (IL-7Rα449F). Thymocytes from these mice overcome a double negative (DN) stage developmental block that allows subsequent T cell maturation and peripheral migration. This is in stark contrast to the severe cytopenia seen in IL-7Rα−/− mice. These findings highlight the importance of IL-7Rα Y449-mediated signals during thymopoiesis, but also indicate a requirement for Y449-independent signals. Infection of IL-7Rα449F mice with the intracellular pathogen Listeria monocytogenes revealed that CD4 and CD8 T cells had different requirements for IL-7Rα signals. Strikingly, CD4 T cells failed to mount a detectable primary response to Listeria. Despite normal CD8 primary responses, maintenance of Listeria-specific CD8 memory was impaired in IL-7Rα449F mice. Furthermore, we show that Bcl-2 is IL-7Rα Y449-independent and insufficient for IL-7-mediated maintenance of CD8 memory. Research funded by the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".