Therapeutic induction of tolerance by IL-10-differentiated dendritic cells in a mouse model of house dust mite-asthma*
Bibliographic record
Abstract
BACKGROUND: It has been reported that retrovirally transduced IL-10-expressing dendritic cells can reverse the asthma phenotype in mice, but that i.v. delivery of dendritic cells differentiated with IL-10 alone (DC10) does not. We report herein DC10 can be highly effective therapeutically in experimental asthma. METHODS: BALB/c mice were sensitized by airway exposure to house dust mite (HDM) without use of adjuvants, then treated with 10⁶ allergen-presenting DC10. We assessed the airway hyperresponsiveness (AHR) to methacholine, circulating levels of IgE and IgG1, and airway recall responses to HDM allergen, including eosinophilia and Th2 cytokines. We also asked whether the DC10 treatments induced tolerance through activation of pulmonary regulatory T cell activities. RESULTS: In vitro, cognate-, but not irrelevant-, allergen-presenting DC10 productively engaged pulmonary Th2-phenotype CD4(+) cells magnetically sorted from HDM-asthmatic mice in Forster (or fluorescence) resonance energy transfer assays. In vivo, treatment of HDM-asthmatic mice with HDM, but not ovalbumin-presenting DC10 abrogated AHR within 4 weeks, and significantly reduced airway eosinophilia, IL-4, IL-5, and IL-13 responses, and circulating HDM-specific IgE and IgG1 levels (each, P ≤ 0.01 versus control mice). CD4(+) CD25(+) Foxp3(+) cells from the lungs of the DC10-treated mice, but not those from asthmatic animals, up-regulated expression of the activated regulatory T cell markers CTLA4 and LAG3, and passive transfer of pulmonary CD4(+) T cells from these mice induced allergen tolerance in HDM-asthmatic recipients. CONCLUSIONS: These findings indicate that allergen-presenting DC10 treatments up-regulate T cell regulatory activities and thereby induce allergen-specific tolerance in a relevant model of human asthma.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".