A34 DEVELOPING A NOVEL MOUSE MODEL TO ELUCIDATE MECHANISMS OF ORAL TOLERANCE IN EARLY LIFE
Bibliographic record
Abstract
Abstract Background Oral tolerance is the active suppression of immune responses to antigens that are first encountered in the gastrointestinal tract. When this process fails, food allergies can arise. Food allergies affect up to 6% of Canadian children underlining the need for a thorough understanding of how oral tolerance develops in childhood. Despite this, tolerance has historically been studied using adult rodent models instead of focusing on more physiologically relevant early-life time points. Aims Our research aims to develop a robust mouse model to elucidate mechanisms of oral tolerance development in early life and we hypothesize that the mesenteric lymph nodes are a major site of food antigen-specific T cell development in early life. Methods Prior to weaning, actively suckling mouse pups were orally gavaged with ovalbumin (OVA), an egg white component and common food allergen or water as a control. Following a series of systemic challenges with OVA, circulating antibody levels were quantified by ELISA to measure the development of oral tolerance to OVA. Additionally, splenocytes isolated from tolerized and control mice were stimulated in vitro with exogenous OVA and cytokines were quantified in culture supernatants via a cytometric bead array assay to assess the suppression of T cell responses to OVA in tolerized mice. One week following oral OVA exposure flow cytometry was used to characterize the expansion of T cell populations in the mesenteric lymph nodes, spleen and thymus. Results Mice orally gavaged with OVA in early life show reduced systemic antibody production after subsequent challenges with OVA, compared to mice not orally exposed to OVA. We determined the minimum dosage of OVA required to confer tolerance in these mice and confirmed the validity of this model in both male and female C57BL/6 and BALB/c mice. Further, we detected an active suppression of IL-5 production, a cytokine indicative of a Type 2 immune response, in OVA-stimulated splenocyte cultures isolated from mice tolerized to OVA. We found a significant increase in the frequency of CD4 T cells in the mesenteric lymph nodes just 1-week following oral OVA exposure. Conclusions We have developed a robust mouse model of oral tolerance where mice are directly exposed to OVA in an early life period while they are still actively ingesting breastmilk, and their mucosal immune system and intestinal microbiota composition are under significant development. To date, our data suggests that the gut draining mesenteric lymph nodes may be a site of food antigen-specific T cell expansion in early life. Funding Agencies CIHRTRIANGLE
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".