Cytokines and inflammatory mediators [24-32]
Bibliographic record
Abstract
Background: Synovitis of rheumatoid arthritis (RA) is characterized by infiltration of innate and adaptive immune cells into the synovial tissue of affected joints.A Th1/Th2 cytokine imbalance with a predominance of Th1 cytokines, including IFNg, is suggested to be a hallmark of RA.Here we examined the spontaneous basal IFNg and IL-10 production of synovial tissue cells (STC) of patients with active RA and the modulatory capacity of separated autologous peripheral blood T-lymphocytes (PB T-cells).Methods: Synovial tissues of 12 patients with RA according to the criteria of the ACR, which presented with a high local inflammatory activity despite appropriate DMARD treatment requiring surgical synovectomy (disease activity score DAS of 2.3 -5.5) were obtained during the surgical procedure, immediately minced and digested with collagenase.STC were used after an overnight culture for ELISPOT assays to determine the frequency of IFNγ or IL-10 producing cells.In order to obtain untouched autologous CD4 and CD8 positive T-cells these were isolated from peripheral blood by the immune rosetting-technique.ELISPOT assays were done with 1x 10 4 STC alone or in co-culture with either 1x10 4 CD4+ or 1x10 4 CD8+ autologous PB T-cells.Cocultures were either left unstimulated or costimulated with a combination of anti-CD3 and anti-CD28 mAb for 24h.Results: Already unstimulated cells isolated from RA synovial tissue exhibited a frequency of 81.3 (mean spot number, ± 48) IFNγ secreting cells after 24h (n=23), while peripheral PBMNC showed no basal IFNγ secretion.No correlation between number of IFNγ producing cells and disease activity was observed.The cocultures of STC with autologous PB T-cells (n=18) resulted in a significant (p<0,01) decrease of the IFNγ frequency (STC + CD4 pos.PB T-cells: 55.7±22.5;STC + CD8 pos.PB T-cells: 63.5±26.2).This results were confirmed in the co-stimulated setting by using anti CD3/CD28 mAb.In contrast in IL-10 ELISPOT there is an increase of IL-10 producing cells in coculture of STC and PB T-cells (n=4) in comparison to STC alone (n=6) (mean number of spots: STC: 27.2; STC + CD4 pos.PB T-cells: 37.8; STC + CD8 pos PB T-cells: 64.7) Conclusions: IFNγ as well as IL-10 secreting cells are demonstrable in RA synovial materials even in unstimulated conditions.Despite abundant synovial T cell infiltrates in some RA patients, both the CD4+ and CD8+ peripheral blood T cells of RA patients provide regulatory effects on the IFNg and IL-10 production of synovial tissue cells.The therapeutic potential of these PB T-cell subsets warrants further investigation. 25.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.012 | 0.005 |
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".