Pro‐tolerogenic effects of photodynamic therapy with TH9402 on dendritic cells
Why this work is in the frame
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Bibliographic record
Abstract
A major goal in transplantation immunology is to develop strategies that can specifically promote tolerance to foreign cells and tissues without compromising other immune functions. Experimental induction of transplantation tolerance by dendritic cells (DCs) and/or T regulatory (Treg) cells can efficiently prevent graft-versus-host disease and organ graft rejection in animal models, and there is much hope that similar strategies in transplanted patients will provide an alternative to immunosuppression. Photodynamic therapy (PDT) is a therapeutic treatment for graft versus host disease and organ rejection that may operate via induction of tolerance. We investigated whether a new PDT therapy, based on exposure of cells to 4,5-dibromorhodamine methyl ester (TH9402), may operate via induction of tolerogenic DC. We developed an in vitro model to mimic the in vivo effect of re-infusing peripheral blood mononuclear cells (PBMCs) treated with PDT based on TH9402 (TH-PDT). TH-PDT-treated PBMCs were co-cultured with allogeneic immature monocyte-derived DCs. After 24 h, the phenotype and T-cell stimulatory capacity of the DCs was assessed. Following phagocytosis of TH-PDT PBMCs, DCs maintained an immature phenotype, produced significantly increased amounts of interleukin-10, and had a reduced allostimulatory capacity in comparison to mature DCs. In the context of transplantation, these data suggest that repeated exposure of circulating DCs to TH-PDT PBMCs may result in presentation of alloantigens under anti-inflammatory conditions and induction of antigen-specific tolerance.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it