Bim regulates allogeneic immune responses and transplant arteriosclerosis through opposing effects on T cell activation and death. (P2218)
Bibliographic record
Abstract
Abstract T cell responses towards allograft arteries are responsible for the development of transplant arteriosclerosis (TA), a vascular condition characterized by intimal thickening of graft arteries. Bim is a pro-apoptotic Bcl-2 protein known to down-regulate immune responses by inducing effector T cell death, but its role in regulating allogeneic T cell responses is poorly understood. We compared allo-activation and death of T cells from Bim+/+, Bim+/- and Bim-/- mice as well as the development of TA in these animals. Unexpectedly, Bim was required for alloantigen-induced proliferation of both CD4 and CD8 T cells, as well as IL-2 production. Partial reduction in Bim expression was sufficient to attenuate T cell activation while complete elimination was required to prevent T cell death driven by cytokine deprivation in vitro. When TA was examined in aortic interposition grafts, intimal thickening was significantly reduced in Bim+/- but not Bim-/- recipients. There was significantly less CD4 T cell accumulation in the intima of arteries from Bim+/- as compared to Bim+/+ recipients, but this effect was not observed in Bim-/- mice. Further, T cell proliferation was significantly reduced in both Bim+/- and Bim-/- mice in response to allograft arteries but T cell death was attenuated only in Bim-/- animals. Taken together, our findings show that Bim controls both T cell activation and death in TA, and that these processes are differentially susceptible to reductions in Bim expression.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.003 | 0.001 |
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".