Differential localization and kinetics of antiviral CD8 T cell responses to chronic and acute murine norovirus infections from initiation onwards
Bibliographic record
Abstract
Abstract Recent global events have highlighted the need to better understand mucosal antiviral immunity. Murine Norovirus (MNV) is small non-enveloped positive sense RNA virus that can be used as a model of intestinal viral infection. In this work we use two highly related MNV strains with distinct biological behaviors; CR6 establishes chronic colonic infection, while CW3 establishes systemic infection initiated in the small intestine and is cleared by day 8, correlating with the peak of cell-mediated adaptive immunity. Using flow cytometry and quantitative immunofluorescent microscopy (QIM) of transgenic P14 CD8 T cells specific to recombinant CR6gp33 and CW3gp33, we characterized CD8 T cell responses to CR6 and CW3 from initiation to clearance of CW3. Our data indicate that initiation of CD8 T cell division in response to CR6 infection is delayed, less robust, and largely limited to the mesenteric lymph nodes (MLNs) with less splenic division compared to CW3 infection. Further, the biogeography of P14 T cell priming differs, as early T cell expansion was restricted to distinct nodes of the MLN complex. These early differences propagate out to the time of CW3 clearance. By day 8, there is differential localization of P14 cells in the GI tract to the site of highest viral load and a larger systemic population of P14 cells following CW3 infection. Infection of MLN-deficient mice revealed a critical role for MLN surveillance in targeting P14 T cells to the GI tract following CR6 infection while the spleen plays a compensatory role in response to CW3. These results show how distinct infectious locations of a continuous mucosal surface influence the responses of antiviral CD8 T cells without confounding effects of antigenicity. This work is supported by the Canadian Institutes for Health Research (CIHR) and a UBC 4 Year Fellowship awarded to Blair K Hardman
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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".