IL-10 reduces CD8 T cell antigen sensitivity during the establishment of chronic viral infection by modifying N-glycan branching
Bibliographic record
Abstract
Chronic viral infections remain a global health concern. The early events that facilitate viral persistence have been linked to the activity of the immunoregulatory cytokine IL-10. However, the mechanisms by which IL-10 facilitates the establishment of chronic infection are not fully understood. Herein, I demonstrate that the antigen sensitivity of CD8 T cells is decreased during chronic infection and that this is directly mediated by IL-10. Mechanistically, we show that IL-10 induces the expression of Mgat5, a glycosyl-transferase that enhances N-glycan branching on surface glycoproteins. Increased N-glycan branching on CD8 T cells promotes the formation of a galectin 3-mediated membrane lattice, which restricts the interaction of key glycoproteins, ultimately increasing the antigenic threshold required for T cell activation. Our study identifies a novel regulatory loop in which IL-10 directly restricts CD8 T cell activation and function through modification of cell surface glycosylation allowing the establishment of chronic infection. This work will inform the design of therapeutics which could serve to better control chronic infections and cancer by maintaining heightened function of effector CD8 T cells.
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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 | 0.001 | 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 | 0.004 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".