IRF2 expression in Tregs limits the antiviral immune response to prevent mortality during chronic infection 3529
Bibliographic record
Abstract
Abstract Description T regulatory cells (Tregs) are vital to limit immunopathology, yet they can also be an immune deterrent during chronic infections. We previously showed IRF2 deletion limits and alters the type I interferon (IFN-I)-induced suppressive program, allowing cells to resist exhaustion. In contrast, IFN-I at onset of viral infection diminishes Treg function to establish an antiviral response. To study IRF2 in Tregs during chronic infection, conditional knockout (cKO) mice with Tregs lacking IRF2 expression were infected with chronic LCMV. Strikingly, ∼50% of cKO mice died in the first 2 weeks of infection. Tregs numbers after infection were rapidly and sustainably reduced in cKO mice, and remaining Tregs exhibited higher IFN-I signaling and an activated phenotype. Surviving cKO mice had better viral control and more functional CD8 T cells versus littermate controls. Lack of IRF2 expression by Tregs reduced CD8 T precursor exhausted (Tpex) and increased the effector virus-specific CD8 T cells early in infection. cKO mice also had more functional virus-specific CD4 T cells with a higher Th1 differentiation early and later in infection. Depletion of all Tregs in otherwise WT mice before infection also showed reduction in survival, but later in infection, showing that the rapid death in the cKO mice is not only due to lower Treg numbers. We are now defining the mechanisms of how IRF2 expression in Tregs leads to CD4 and CD8 T cell exhaustion, and prevents mortality in chronic infection. Topic Categories Viral Immunology (VIR)
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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) | 0.002 | 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".