SHIP-deficient dendritic cells suppress T cell proliferation via a nitric oxide independent mechanism (91.9)
Bibliographic record
Abstract
Abstract Dendritic cells (DCs) are potent stimulators of the immune system but can also be powerful inducers of tolerance. Previous studies have shown that myeloid DC precursors are capable of suppressing T cell proliferation through a contact and nitric oxide (NO) -dependent mechanism. In addition, GM + IL-4, but not Flt3L, -derived DCs have been reported to suppress T cell proliferation by inducing T cell apoptosis. The SH2-containing inositol 5’-phosphatase (SHIP) is a potent suppressor of the PI3K pathway with known functions in regulating myeloid cell development and survival. However, little is known of SHIP’s role in the suppressive ability of DC subsets. In this study we co-cultured polyclonally activated T cells with bone marrow derived DCs or DCs isolated from the spleens of WT and SHIP-/- mice to determine SHIP’s role in DC-induced T cell suppression. We found that both WT and SHIP-deficient DCs derived with GM-CSF ± IL-4 profoundly suppress T cell proliferation while Flt3L-derived and splenic DCs do not. The mechanism of suppression proved to be contact dependent for WT and SHIP-deficient GM-CSF DCs. However, unlike WT, SHIP-deficient DCs do not produce detectable levels of NO. These results suggest a novel mechanism of myeloid DC-induced T cell suppression at work in SHIP-deficient DCs. This research is funded by an NCIC grant held by GK.
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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) | 0.002 | 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".