CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells suppress γδ T‐cell effector functions in a model of T‐cell‐induced mucosal inflammation
Bibliographic record
Abstract
CD4(+) CD25(+) Foxp3(+) regulatory T (T(REG) ) cells are critical mediators of peripheral immune tolerance, and abrogation of their function provokes a variety of autoimmune and inflammatory states including inflammatory bowel disease. In this study, we investigate the functional dynamics of T(REG) -cell responses in a CD4(+) T-cell-induced model of intestinal inflammation in αβ T-cell-deficient (TCR-β(-/-) ) hosts to gain insights into the mechanism and cellular targets of suppression in vivo. We show that CD4(+) T effector cell transfer into T-cell-deficient mice rapidly induces mucosal inflammation and colitis development, which is associated with prominent Th1 and Th17 responses. Interestingly, we unveil a prominent role for resident γδ T cells in mucosal inflammation as they promote Th1 and particularly Th17 responses in the early phase of inflammation, thus exacerbating colitis development. We further demonstrate that CD4(+) CD25(+) Foxp3(+) T(REG) cells readily inhibit these responses and mediate disease protection, which correlates with their accumulation in the draining LN and lamina propria. Moreover, T(REG) cells can directly suppress γδ T-cell expansion and cytokine production in vitro and in vivo, suggesting a pathogenic role of γδ T cells in intestinal inflammation. Thus, functional alterations in T(REG) cells provoke dysregulated CD4(+) and γδ T-cell responses to commensal antigens in the intestine.
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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) | 0.001 | 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) | 0.001 | 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".