IMMUNE MODULATION AND PREVENTION OF ALLOGENEIC GRAFT REJECTION BY THERAPEUTIC DENDRITIC CELLS
Bibliographic record
Abstract
O334 Purpose: Tolerogenic dendritic cells (Tol-DC) play an important role in transplant tolerance through initiating a self-maintaining regulatory feedback loop with CD4+ CD25+ T regulatory cells (Treg) (J Immunol 2003, 170:1304) based on experiments in vitro. This study was designed to evaluate the in vivo immunomodulatory ability of Tol-DC using a murine allogeneic heart transplant model. Methods: Dendritic cells were cultured from donor strain (C57/BL6, H-2b) bone marrow progenitors. Tol-DC were generated by culture in medium conditioned with LF15-0195, a tolerance-inducing NF-κB inhibitor. Intravenous administration of Tol-DC to recipients (Balb/c, H-2d) was performed 7 days prior to MHC-fully mismatched heterotopic heart transplantation. The abilities of Tol-DC to induce immune modulation were assessed in vitro and in vivo. Results: In vitro-generated Tol-DC possessed tolerogenic properties as measured by decreased expression of MHC II and co-stimulatory molecules, as well as, impaired allo-stimulatory capacities. Administration of in vitro-generated Tol-DC (5x106 cells) prior to transplantation resulted in significant prolongation of allograft survival (MST 48 ± 14 days), as compared to the survival of recipients treated with the same number of control DC (MST 13 ± 1 day). In addition, CD4+CD25+ T cells were significantly increased in the Tol-DC treated recipients but not in control DC treated recipients. CD4+CD25+ T cells isolated from Tol-DC treated recipients had regulatory ability in an in vitro inhibitory MLR assay. Furthermore, the cytokine profile of T cells in the Tol-DC treated recipients revealed a Th2 differentiation. Conclusions: In vitro-generated Tol-DC initiate a regulatory feedback loop in vivo through promotion of Treg generation and Th2 differentiation, which subsequently prevents allograft rejection. This study was partially supported by Heart and Stroke Foundation of Canada, Roche Organ Transplantation Research Foundation, The Kidney Foundation of Canada, and by MOTS Research Fund in London Health Sciences Centre.
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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) | 0.001 | 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".