PD-1 expression is required in recent thymic emigrants to establish systemic self-tolerance (143.15)
Bibliographic record
Abstract
Abstract Homeostatic activation of T cells occurs in both natural and artificially induced states of lymphopenia. Control of this process may be particularly important during the period when the first T cells are exported from the thymus, as recent thymic emigrants (RTE) have a heightened sensitivity to homeostatic cytokines. We tested whether PD-1 is required to prevent lymphopenia-induced immunopathology, and assessed its importance in recent thymic emigrants vs. established peripheral T cells. Established T cells express low levels of PD-1 and established PD-1-/- T cells did not cause overt disease in lymphopenic Rag-/- recipients. In contrast, PD-1 was expressed at high levels on RTE, and PD-1-/- RTE produced from hematopoietic stem cells (HSC) generated a rapidly lethal multi-organ inflammatory disease in the Rag-/- recipients. Disease could be blocked by increasing competition through co-transfer of wild type HSC or by using cytokine receptor deficient or neonatal recipients that have reduced lymphoid space for homeostatic activation. Thus, the PD-1 pathway has a broadly important role in self-tolerance, controlling a key checkpoint in the prevention of lymphopenia driven autoimmunity by RTE. Clinical therapies for autoimmune disease employing lymphoablation and hematopoietic stem cell transplantation will need to take into account functional polymorphisms in the PD-1 pathway, if the treatment is to ameliorate rather than exacerbate autoimmunity.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".