In vitro PTEN deletion in peripheral T cells enhances activation but does not replace CD28 costimulation or prevent anergy (35.37)
Bibliographic record
Abstract
Abstract PTEN plays a pivotal role in T cell development by negatively regulating the PI3K signaling pathway important for activation, growth, and proliferation. In Cre/loxp mouse models when PTEN is deleted during thymogenesis, peripheral T cells show CD28-independent IL-2 production and are relatively resistant to anergy induction. These animals also develop autoimmunity and T cell lymphomas. However, the consequences of PTEN deletion directly in peripheral T cells are not known, and we hypothesized that much of this phenotype might be explained by the elimination of PTEN during thymic development. The use of CAR Tg-PTENflox/flox mice allowed deletion of PTEN using a Cre adenovirus in vitro. PTEN-deleted splenic T cells or Th1 clones exhibited enhanced IL-2 and IFN-gamma production and proliferation upon TCR/CD28 engagement. Gene expression profiling revealed a subset of induced genes that were augmented upon PTEN deletion. However, PTEN-deficient T cells still required CD28 costimulation for IL-2 production and were not resistant to anti-CD3-induced anergy. Our results indicate that deletion of PTEN can augment the activation of post-thymic T cells but does not mediate CD28-independence or anergy resistance. Ongoing experiments will determine if the absence of PTEN protein in post thymic T cells will lead to improved immune responses in vivo, and if overt autoimmunity or lymphomagenesis will occur.
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".