Comparison of Dexamethasone and Cyclosporine to selective protein Kinase C-theta inhibitor effects on blood IL-2 production and T cell activation (35.32)
Bibliographic record
Abstract
Abstract Protein kinase C-theta (PKCθ) is critical in T cell IL-2 production upon TCR stimulation, making PKCθ an attractive drug target for inflammatory diseases. Our goal was to compare the effects of PKCθ selective blockade to alternative immune modulators dexamethasone (Dex) and cyclosporine A (CsA). Compound A, a selective PKCθ inhibitor, was evaluated on T cell responses following co-stimulation in vitro. With pre-activated CD4+ T cells, both Compound A and CsA reduced IL-2 production with comparable potency. However, CsA inhibited T cell proliferation with 10 fold higher potency than Compound A. Dex was the least potent on T cells but was effective in blocking IL-2 production in human whole blood. Next we examined whether exposure to Compound A or CsA in a primary activation would affect the ability of T cells to respond to secondary TCR stimulation. Both Compound A and CsA reduced T cell proliferation upon re-stimulation. Exogenous IL-2 restored the proliferation for Compound A exposed T cells, but not for CsA exposed T cells. We confirmed that Compound A-treated T cells had higher CD25 expression relative to those treated with CsA, accounting for their greater IL-2 responsiveness. Taken together, these findings indicate that targeting PKCθ impairs T cell IL-2 production, but not IL-2 responsiveness, suggesting that this inhibitor may selectively modulate T cell responsiveness under specific activation conditions.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".