NKG2D-Mediated Cytotoxicity toward Oligodendrocytes Suggests a Mechanism for Tissue Injury in Multiple Sclerosis
Bibliographic record
Abstract
NKG2D is an activating or coactivating receptor expressed on human natural killer (NK) cells, CD8+ T cells, and gamma/delta T cells. NKG2D ligands have been detected on many tumor cell types and can be induced on nontransformed cells by environmental signals including DNA damage and inflammation. We investigated the contribution of NKG2D-NKG2D ligand interaction on CNS-directed immune responses. We observed that primary cultures of human adult oligodendrocytes and fetal astrocytes expressed ligands for NKG2D in vitro whereas neurons, microglia, and adult astrocytes did not. Disruption of the NKG2D-NKG2D ligand interaction using blocking antibodies significantly inhibited killing of primary human oligodendrocytes mediated by activated human NK cells, gamma/delta T cells, and allo-reactive CD8+ T cells. NKG2D ligands [major histocompatibility complex class I chain-related molecules A and B (MICA/B)] were detected in groups of cells and colocalized with an oligodendrocyte marker (adenomatous polyposis coli) in white matter sections obtained from multiple sclerosis lesions but not in normal control samples. CD8+ T cells could be detected in close proximity to MICA/B+ cells within multiple sclerosis lesions, supporting an in vivo interaction between these immune effectors and stressed MICA/B-expressing oligodendrocytes. These results imply that NKG2D-NKG2D ligand interaction can potentially contribute to cytotoxic responses mediated by activated immune effector cells in the inflamed CNS, as observed in multiple sclerosis.
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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 | 0.002 |
| 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) | 0.000 | 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".