Long-Term Tolerance and Skin Allograft Survival in CD200tg Mice After Autologous Marrow Transplantation
Bibliographic record
Abstract
BACKGROUND: CD200 overexpression in transgenic recipients, or by tissue allografts, increases skin and cardiac graft survival in mice receiving rapamycin, in association with increased Foxp3(+)Treg graft infiltration. However, less than 50% of skin grafts persist beyond 25 days. We investigated whether immune ablation using busulphan and cyclophosphamide, followed by autologous marrow reconstitution, would permit long-term survival in a greater percentage of recipients and induce tolerance, allowing for withdrawal of immunosuppressive drugs. METHODS: C57BL/6 wild type (BL/6 WT) or CD200(tg) mice received BALB/c skin grafts with rapamycin (1 mg/kg/36 hr) for 7 days. Thereafter, subgroups received busulphan or cyclophospamide for 6 days, followed by BL/6 marrow transplantation (BMTx), whereas controls were maintained on rapamycin. Beginning 7 days after marrow transplantation, mice receiving BMTx also received rapamycin for a further 7, 14, or 21 days (to a maximum of 42 days after transplantation) after which times, all immunosuppressions were withdrawn. Graft survival was monitored throughout, and mixed leukocyte cultures (MLCs) (using peripheral blood leukocytes) were performed for all groups at 60 days after transplantation. Gene expression was performed in grafts harvested at 80 days. RESULTS: Although all WT mice rejected grafts by 16 days, survival in CD200(tg) was approximately 40% at 60 days, with antigen-specific decreased MLC responses to BALB/c. After BMTx, survival in WT mice was greater than 40% at 60 days, and greater than 90% at 60 days in CD200(tg), with corresponding attenuated MLC responses. Long-term surviving grafts were infiltrated by Tregs of both host and donor marrow origins, as defined using CD45 congeneic donors or recipients. Survival was increased by infusion of an antibody directed to TNFRSF25 on Tregs. CONCLUSION: Autologous BMTx improves graft survival and promotes graft tolerance.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".