Class II transactivator knockdown limits major histocompatibility complex II expression, diminishes immune rejection, and improves survival of allogeneic bone marrow stem cells in the infarcted heart
Bibliographic record
Abstract
This study was performed to investigate how to overcome immunorejection associated with allogeneic stem cell therapy in the infarcted heart. Allogeneic bone marrow mesenchymal stem cell (MSC) differentiation increases major histocompatibility complex II (MHC II) expression, inducing transition from immunoprivileged to immunogenic phenotype. MHC II expression is regulated by the class II transactivator (CIITA). We isolated and characterized mouse and human MSCs and knocked down CIITA expression. Wild-type (WT) or CIITA-knockout (CIITA(-)) mouse MSCs were implanted into infarcted mouse myocardia, and recipient allo-antibody formation, cell survival, and cardiac function were measured. WT mouse and human MSCs that were myogenically differentiated showed increased MHC II and CIITA expression. Differentiated CIITA(-) MSCs lacked MHC II induction and showed reduced cytotoxicity in allogeneic leukocyte coculture. Differentiation of human MSCs increased MHC II expression, which resulted in cytotoxicity in allogeneic leukocyte coculture and was prevented by CIITA small interfering RNA. In contrast to WT MSCs, CIITA(-) MSCs did not initiate recipient allo-antibody formation and instead survived in the injured myocardium and significantly improved ventricular function. Decreasing CIITA expression in allogeneic MSCs abolished MHC II induction during myogenic differentiation and prevented immunorejection of these cells from the infarcted myocardium, which enhanced beneficial functional effects of MSC implantation on myocardial repair.-Huang, X.-P., Ludke, A., Dhingra, S., Guo, J., Sun, Z., Zhang, L., Weisel, R. D., Li, R.-K. Class II transactivator knockdown limits major histocompatibility complex II expression, diminishes immune rejection, and improves survival of allogeneic bone marrow stem cells in the infarcted heart.
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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".