PD-1 controls effectors but not the generation or function of natural or induced regulatory T-cells (P1011)
Bibliographic record
Abstract
Abstract During T cell activation, the balance of co-stimulatory and co-inhibitory interactions plays an important role in shaping the resulting T cell response. Co-inhibitory signals help maintain peripheral immune tolerance, and thus animals with defective co-inhibitory molecules, such as PD-1 KO mice, are predisposed to autoimmunity. Unlike PD-1 KO mice, which develop mild autoimmunity, adult Rag KO recipients of PD-1 KO hematopoietic stem cells (HSC) succumb to rapid and severe multi-organ autoimmune disease soon after T cells first emerge from the thymus, implicating PD-1 as a critical factor in the control of T cell self-reactivity during lymphopenia induced homeostatic proliferation (LIP). While we have found no reduction in the absolute number of FoxP3+ regulatory T cells (Treg) in diseased PD-1 KO vs. wild type (WT) HSC recipients, some studies have indirectly suggested that PD-1 deficiency may inhibit the development of induced Treg (iTreg) cells from conventional T cells in the periphery. We therefore investigated whether PD-1 deficiency results in an intrinsic inability of T cells to convert to iTreg in vivo, which could lead to disease in PD-1 KO HSC recipients. Surprisingly, our findings suggest that PD-1 deficiency does not inhibit the development of iTreg nor does it affect Treg suppressive function, and that in the context of LIP, co-inhibitor deficient effector T cells cause disease primarily by expanding beyond the ability of Treg to control them.
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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".