CXCR4 and CXCR6 dually limit T cell entry into the polyomavirus-infected brain
Bibliographic record
Abstract
T cell responses are vital for controlling viral infection in the central nervous system (CNS), but must be tightly regulated to limit tissue-damaging inflammation. Using mouse polyomavirus (MuPyV) CNS infection, an in vivo model for JCPyV-induced Progressive Multifocal Leukoencephalopathy (PML), we investigated sites of early infection, immune responses, and recruitment of T cells to the brain. Multiplexed error-robust fluorescence in situ hybridization (MERFISH) single-cell spatial transcriptomics was applied to assess the regionality of virus infection and brain-resident cell and infiltrating leukocyte responses. MERFISH, immunofluorescence microscopy, quantitative PCR, and flow cytometry demonstrate that the ependyma is the predominant region of MuPyV CNS infection and localization of T cells, and implicated CXCR4 and CXCR6 in T cell migration to the ependyma and subventricular zone. Using CXCR6 knockout mice and a specific CXCR4 small molecule antagonist, we found that the combined impairment of CXCR6 and CXCR4 signaling resulted in elevated infiltration of T cells in the MuPyV-infected brain. This work demonstrates that CXCR4 and CXCR6 act in a nonredundant fashion to restrict T cell accumulation to the polyomavirus-infected ependyma, with important implications for ongoing efforts to use JCPyV-specific T cell adoptive immunotherapy for PML.
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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 | 0.000 | 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) | 0.000 | 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 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".