CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of <i>Leishmania major</i> infection favors pathogen persistence
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Pathogen persistence after clinical cure is a hallmark of many chronic infections. Previously, we showed that naturally occurring CD4+CD25+ regulatory T (nTreg) cells rapidly accumulate within chronic dermal sites of Leishmania major infection where they suppress anti-pathogen CD4+ T cell responses, favor parasite persistence and dermal pathology, and consequently control concomitant immunity. Here, we postulated that chemokines might direct nTreg cell homing in sites of infection and show that CD4+CD25+ nTreg cells, compared with normal CD4+ T cells, preferentially express the CCR5 chemokine receptor, which enables them to migrate in response to CCR5 ligands in vitro. We show that in contrast to their wild-type (WT) counterparts, CCR5-/- CD4+CD25+ nTreg cells resulted in an increased magnitude of parasite-specific, interferon gamma-producing CD4+ T cells within infection sites, dramatically reduced parasite numbers, and potent resistance to infection, a finding consistent with the clinical outcome of infected CCR5-/- mice. Interestingly, this resistance was related to an inefficient migration of CCR5-/- nTreg cells to infected dermal sites compared with WT nTreg cells. Thus, this study shows that CCR5 directs the homing of CD4+CD25+ nTreg cells to L. major-infected dermal sites where they promote the establishment of infection and long-term survival of the parasite in the immune host.
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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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it