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 IFN 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) IFN secreting cells after 24h (n=23), while peripheral PBMNC showed no basal IFN secretion. No correlation between number of IFN 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 IFN frequency (STC + CD4 pos. PB T-cells: 55.722.5; STC + CD8 pos. PB T-cells: 63.526.2). 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: IFN 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".