Cellular Dynamics of Immune Evasion during <i>Leishmania major</i> infection
Bibliographic record
Abstract
Abstract Infection by Leishmania major generates a strong T cell response, yet clearance is incomplete. Understanding of persistence mechanisms is still lacking, but Leishmania major mediated suppression of antigen presentation mechanisms and the presence of regulatory T cells within the lesion site have been proposed to prevent parasite clearance in vivo. Here, we used a novel TCR transgenic mouse model, where CD4+ T cells recognize an immunodominant peptide derived from Leishmania-glycosomal phosphoenolpyruvate carboxykinase (PEPCK), to visually characterize anti-L. major CD4+ T cell responses both in vitro and in vivo during acute and persistent infection. We confirmed that PEPCK T cells engage in prolonged interactions with infected macrophages, which resulted in high IFNg production. Effector T cell responses were significantly suppressed by PEPCK-specific, but not polyclonal Tregs, indicating that antigen recognition is required for their suppressive activity. High suppressive activity by Tregs correlated with high IL-10 expression and lower IL-12, TNF, and IL-2 production. Finally, adoptive transfer of PEPCK effector T cells into infected mice led to their recruitment into lesion sites, displaying cellular behaviours consistent with antigen recognition. We are currently characterizing whether effector T cell responses are altered in healed lesions, where persistently-infected cells are readily observed. Collectively, our microscopy-based approach will better define effector T cell responses during acute infection, and mechanistic understanding of how Tregs promote parasite persistence within healed skin.
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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) | 0.000 | 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 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".