Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation
Bibliographic record
Abstract
Tumor necrosis factor (TNF)‐like cytokine (TL1A) is a T‐cell costimulator that bolsters cyto‐kine‐induced activation through death receptor 3 (DR3). To explore the relationship between T‐cell activation and TL1A responsiveness, flow cytometry profiled DR3 expression in resting and activated T cells. In human CD4 + T cells, DR3 was induced rapidly following activation and expressed prominently by in‐terleukin (IL)‐17‐secreting T cells (Th17). Splenic T cells from wild‐type and DR3‐deficient mice showed that TL1A activation of DR3 inhibits Th17 generation (81 ±2.6% at 100 ng/ml TL1A) from naive T cells. This response was not associated with suppression of T‐cell proliferation. Using neutralizing antibodies or T cells derived from genetically modified mice, TL1A inhibition of Th17 development was found to be independent of IL‐2, IL‐27, γIFN, IFNAR1, and STAT1. Under suboptimal TCR activation, TL1A continued to block IL‐17A secretion, however, the reduced threshold of TCR engagement was now linked with an increase in TL1A‐driven proliferation. In contrast, fully committed Th17 cells displayed an altered TL1A responsiveness and in the absence of TCR costimulation supported the maintenance of T cell IL‐17A expression. Consequently, TL1A orchestrates unique outcomes in naive and effector T‐helper cells, which may affect the proliferation, differentiation and maintenance of Th17 cells in peripheral compartments and inflamed tissues.—Jones, G. W., Stumhofer, J. S., Foster, T., Twohig, J.P., Hertzog, P., Topley, N., Williams, A. S., Hunter, C. A., Jenkins, B. J., Wang, E. C. Y., Jones, S. A. Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation. FASEBJ. 25, 409–419 (2011). www.fasebj.org
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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 | 0.001 | 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) | 0.000 | 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".