Differential expression of mannose-6-phosphate receptor regulates T cell contraction
Bibliographic record
Abstract
CD8(+) T cells provide protection against pathogens and cancer. After encountering a pathogenic antigen, CD8(+) T cells undergo a triphasic program of rapid proliferation, contraction, and memory formation. Most (∼90-95%) CD8(+) T cells die after vigorous proliferation in the T cell contraction phase, yet the mechanism that triggers apoptotic T cell death remains elusive. This study tested the hypothesis that differential cell-surface expression of M6PR, a multifunctional receptor that regulates lysozyme biogenesis, but also uptakes apoptosis-inducing serine-protease Gzm-B, critically determines life vs. death decisions in T cells. We demonstrate that M6PR-expression on CD8(+) T cell surfaces is dynamically regulated during LmOVA bacterial infection. Notably, time-lapse, confocal microscopy and flow cytometry confirms that M6PR(low) effectors, but not M6PR(high) effectors, escape Gzm-B lethal-hit derived from CD4(+)25(+) Treg cells. Adoptive cotransfer of M6PR(low) effectors and M6PR(high) effectors sorted from LmOVA-infected, congenic mice at the peak of CD8(+) T cell response, reveals that M6PR(low) effectors with the CD8(+) T cell memory precursor phenotype preferentially survive the CD8(+) T cell contraction and differentiate into functional, long-lasting memory CD8(+) T cells. Taken together, our data provide the first evidence, to our knowledge, that selective M6PR down-regulation has a critical role in CD8(+) T cell survival, and our findings have implications for efficient vaccine design and immunotherapy.
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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) | 0.001 | 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 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".