T‐bet interferes with PD‐1/PD‐L1‐mediated suppression of CD4<sup>+</sup> T cell inflammation and survival in Crohn's disease
Bibliographic record
Abstract
Abstract Pathogenic inflammation mediated by overactive type 1 helper T cell (Th1) responses could exacerbate and perpetuate Crohn's disease. Programmed death (PD)‐1 and its ligand PD‐L1 pathway could be upregulated to suppress inflammation. We wondered why this pathway is ineffective at suppressing pathogenic Th1 inflammation in Crohn's disease patients. Here, we found that overexpression of T‐bet via transfection significantly reduced the expression of PD‐1. PD‐L1 was capable of suppression proinflammatory CD4 + T cells, but T‐bet transfection significantly reduced the susceptibility of CD4 + T cells toward PD‐L1‐mediated suppression, evidenced by the observations that at low PD‐L1 concentration T‐bet transfected and mock transfected CD4 + T cells presented comparable IL‐2 production, but at high PD‐L1 concentration, T‐bet transfected CD4 + T cells presented significantly higher IL‐2 than mock transfected CD4 + T cells. PD‐L1 could significantly reduce the survival of CD4 + T cells from Crohn's disease patients, but interestingly, in the absence of PD‐L1, the survival was better in mock transfected CD4 + T cells, while in the presence of PD‐L1, the survival was better in T‐bet transfected CD4 + T cells. Crohn's disease patients with greater severity presented higher T‐bet expression and lower PD‐1 expression in CD4 + T cells, demonstrating an association between T‐bet expression and disease progression. We also discovered that stimulation with bacterial antigens could upregulate the expression of T‐bet. Together, this study demonstrated that T‐bet overexpression could interfere with PD‐1/PD‐L1‐mediated suppression of CD4 + T cell inflammation and survival, and potentially contributed to the development and persistence of Crohn's disease.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".