Initiation of food allergy by a CD4+ T cell-intrinsic IL-4 program, controlled by OX40L (P6204)
Bibliographic record
Abstract
Abstract Intestinal Th2 immunity in food allergy results in the production of IgG1 and IgE, and upon antigen challenge, anaphylaxis and eosinophilic inflammation. Although allergic sensitization critically requires IL-4 to develop, the source and control of IL-4 during the initiation of Th2 immunity remains unclear. Non-intestinal and non-food allergy systems have suggested a role for innate lymphocytes such as NKT or γδ T cells as a rapid source of IL-4 required to induce Th2 polarization. In contrast, we show here that NKT-deficient IL-15 KO, β2m KO and anti-NK1.1 treated mice have completely intact Th2 food allergic responses comparable to NKT-sufficient mice, including antigen-specific IgG1 and IgE, anaphylaxis, eosinophilic inflammation and cytokine production. Likewise, γδ T cell-deficient TCRδ KO mice mount comparable Th2 immune responses to oral antigen as their WT counterparts. By restricting IL-4 expression to only CD4+ Th cells, we find that IL-4 from CD4+ Th cells themselves induce food allergy. Further, IL-4 reporter mice show that CD4+ Th cell production of IL-4 in vivo is dependent on OX40L, a costimulatory molecule that we have shown to be highly expressed on allergen-exposed dendritic cells (DCs). Although NKT and γδ T cells express IL-4, this is not upregulated after allergen priming. Together, these data show that intestinal Th2 immunity in food allergy is initiated by a CD4+ Th cell-intrinsic IL-4 program that is controlled by DC-OX40L and not NKT or γδ T cells.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".