Cytotoxic T lymphocytes express intracellular stores of FasL via mechanisms distinct from cytolytic granule exocytosis (B16)
Bibliographic record
Abstract
Abstract Cytotoxic T lymphocytes (CTL) lyse target cells through the release of cytolytic granules and cell surface expression of Fas ligand (FasL). We found that there is prestored FasL pool in CTL, which underwent rapid TCR-regulated cell surface expression upon target cell engagement. Current models suggest that FasL is stored in cytolytic granules and that FasL cell surface expression would be subject to the same control as degranulation. The aim of the current study is to investigate if degranulation of cytolytic granules and FasL expression pathways of CTL are controlled by differential mechanisms. FasL cell surface expression and degranulation, as measured by CD107a cell surface expression in CTLs were compared by flow cytometry under different conditions. FasL underwent an immediate and transient cell surface delivery following either TCR stimulation by anti-CD3 antibody crosslinking, or phorbol ester treatment, conditions that do not permit degranulation. Furthermore, treatment with pharmacological reagents indicated that the preformed FasL cell surface transport is PI3-kinase (PI3K)-, calcineurin- and microtubule-independent, which are all indispensable for degranulation. Finally, stored FasL resides in vesicles distinct from cytolytic granules as assessed by confocal microscopy and subcellular fractionation. Our data clearly show that CTL degranulation and FasL lytic mechanisms are fully independent with respect to regulation and localization. This work was funded by the Canadian Institutes of Health Research (CIHR).
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".