Persistent antigen is essential for sustaining <i>Leishmania</i> -specific memory CD4 <sup>+</sup> T cells and long-term immunity
Bibliographic record
Abstract
Abstract Memory T cells are critical for secondary immunity against pathogens, yet their persistence in the absence of antigen remains unclear. While memory CD8 + T cells are known to persist independently of their cognate antigen, the durability of memory CD4 + T cells in the absence of antigen remains controversial. Recovery from cutaneous leishmaniasis confers lifelong immunity, largely mediated by CD4 + T cells, but the necessity of persistent parasites for sustaining this immunity has not been empirically confirmed. We investigated immunity in mice infected with a dihydrofolate reductase-thymidylate synthase ( dhfr-ts )-deficient Leishmania major , which cannot persist due to their thymidine salvage deficiency. These mice lost protection against wild-type challenge, correlating with a decline in Leishmania (PEPCK)-specific CD4 + T cells. To further dissect this relationship, we generated PEPCK-specific CD4 + TCR transgenic (PEG) mice, enabling precise tracking of Leishmania -specific memory CD4 + T cells. Both in vitro and in vivo -generated memory PEG cells gradually disappeared over time in the absence of antigen, irrespective of the host’s MHC II status, and this loss paralleled the erosion of infection-induced immunity. PEG and endogenous PEPCK-specific memory cells were not maintained in mice infected with dhfr-ts - or PEPCK -deficient L. major , resulting in loss of recall responses and secondary immunity. These findings demonstrate that continuous antigen presence is crucial for maintaining Leishmania -specific memory CD4 + T cells and highlight the role of persistent antigen in sustaining long-term immunity against chronic infections.
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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 | 0.001 |
| 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 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".