Prolongation of Cardiac Allograft Survival by Rapamycin and the Invariant Natural Killer T Cell Glycolipid Agonist OCH
Bibliographic record
Abstract
BACKGROUND: Invariant natural killer T (iNKT) cells are glycolipid-responsive cells with potent immunomodulatory properties. Although iNKT cells have been implicated in cardiac allograft tolerance, whether in vivo triggering of iNKT cells with Th2-promoting glycolipids offers a therapeutic benefit in heart transplantation remains unexplored. METHODS: C3H (H-2k) hearts were transplanted into C57BL/6 (H-2b) mice. The recipients were left untreated or received the Th2-promoting iNKT cell agonist OCH, the antirejection agent rapamycin, or both. Allografts were recovered on postoperative day 8 or at endpoint, stained with hematoxylin-eosin, and analyzed for intragraft transcript levels of effector cytokines and iNKT cells' invariant T-cell receptor segment Valpha14-Jalpha18. The presence of circulating alloantibodies was assessed in recipients' sera at similar time points. A second fully mismatched cardiac allograft model (BALB/c-to-C57BL/6) was used to further validate the efficacy of our treatment regimens. RESULTS: Combination immunotherapy with OCH and rapamycin significantly enhanced C3H allograft survival and led to nearly normal graft histology with minimal vascular changes and mononuclear cell infiltration, and an almost normal IgG1:IgG2a ratio in recipients' sera. These were accompanied by elevated intragraft mRNA levels of interleukin (IL)-4, and to a lesser extent IL-10 and IL-13, and high transcript levels of Valpha14-Jalpha18 T-cell receptor gene segment. Furthermore, when used alone or together with rapamycin, OCH delayed allograft rejection in our BALB/c-to-C57BL/6 model. CONCLUSIONS: In vivo administration of OCH may deviate alloimmune responses towards a Th2 phenotype and prolong allograft survival. Select iNKT cell glycolipid agonists can therefore be used in monotherapy or combination immunotherapy of transplant rejection.
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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 | 0.000 |
| 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 | 0.001 |
| 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".