The Degree of Phylogenetic Disparity of Islet Grafts Dictates the Reliance on Indirect CD4 T-Cell Antigen Recognition for Rejection
Bibliographic record
Abstract
Cellular xenograft rejection involves a pronounced contribution of CD4 T-cells recognizing antigens in association with recipient MHC class II molecules. However, the requirement for such "indirect" antigen recognition for acute islet xenograft is not clear, especially as a function of the phylogenetic disparity between the donor and recipient species. In vitro studies show that C57BL/6 (B6) mouse T-cells respond directly to either allogeneic BALB/c or phylogenetically related xenogeneic WF rat stimulator cells while having undetectable responses to phylogenetically disparate porcine stimulator cells. Although all types of grafts rejected acutely in wild-type mice, this response demonstrated markedly differing dependence on host MHC class II antigen presentation, depending on the donor species. While BALB/c islet allografts were acutely rejected in B6 MHC class II-deficient (C2D) recipients, WF rat xenografts demonstrated marked prolongation in C2D hosts relative to wild-type recipients. Interestingly, neonatal porcine islet (NPI) xenografts uniformly survived long term (>100 days) in untreated C2D hosts despite transfer of wild-type CD4 T-cells, demonstrating that survival in C2D recipients was not secondary to a lack of CD4 T-cells seen in such mice. Taken together, these results show a marked hierarchy in the requirement for host MHC class II-restricted indirect pathway in the rejection of pancreatic islet grafts. Thus, while cellular rejection of porcine xenografts is generally quite vigorous, this pathway is relatively finite, displaying a major reliance on host MHC class II-dependent antigen presentation for acute rejection.
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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 | 0.000 |
| 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".