CD8 T Cells Target Antigen Cross-Presented by Bone Marrow Derived Cells to Induce Bystander Rejection of Grafts Lacking the Cognate Peptide-MHC
Bibliographic record
Abstract
CD8 T cells play a key role in cancer immunotherapy and allograft rejection. However, it is not clear how they kill cells and tissues that do not have the agonist peptide-major histocompatibility complex (MHC) on their surface, as in the settings of MHC class I deficient tumors and indirect rejection of MHC-mismatched transplants. CD8 T cells might respond to agonist antigen cross-presented on hematopoietic cells, leading to a "bystander" rejection. Alternatively, they may recognize agonist antigen cross-presented on recipient endothelial cells and kill the tissue's vital blood supply. The latter mechanism predicts that all non-vascularized grafts, grafts dependent on in-growth of recipient blood vessels, will be susceptible to CD8 T cell mediated indirect rejection. In contrast, we show here that non-vascularized transplants, bearing the same agonist antigen, are not universally susceptible to this rejection pathway. Non-vascularized skin, but not islet or heart tissue transplants were indirectly rejected by CD8 T cells. Furthermore, CD8 T cells were able to indirectly reject skin grafts when recipient MHC class I expression was restricted to bone marrow derived cells but not when it was restricted to radioresistant cells (e.g. endothelial cells). These findings argue against a major role for endothelial cell cross-presentation in killing of tissue that does not present the agonist peptide-MHC class I. Instead, the data suggests that cross-presentation by recipient hematopoietic cells underlies the CD8 T cell mediated killing of tissue that is unable to directly present the target peptide-MHC class I.
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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 | 0.001 | 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 | 0.001 | 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 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".