GITR sustains IL-2+ CD4 helper T cells to facilitate early control of a chronic viral infection (IRC7P.422)
Bibliographic record
Abstract
Abstract CD4 T cells are critical for control of persistent infections; however, the key signals that regulate CD4 T help during infection remain incompletely defined. Here we show that during lymphocytic choriomeningitis virus (LCMV) clone 13 infection, glucocorticoid-induced TNFR (GITR)-deficient mice exhibit defective CTL responses and viral control. Differences in CTL responses and viral control between GITR+/+ and GITR-/- mice were lost when CD4 T cells were depleted. Furthermore, mixed bone marrow chimeric mice and transfer of LCMV-specific CD4 or CD8 T cells demonstrated that these effects of GITR are CD4 T cell-intrinsic. GITR is dispensable for initial CD4 T cell proliferation and differentiation, but supports the post-priming accumulation of IL-2+ Th1 cells to facilitate CTL expansion and early viral control. In vivo GITR-dependent activation of p65 NF-kB and S6 ribosomal protein was detected at day 3 p.i., a time at which GITR-L is maximally expressed on macrophages. Defects in CD4 T cell accumulation in GITR-deficient T cells were apparent starting at day 5 p.i. Consistently, we pinpoint IL-2-dependent CD4 T cell help for CTLs to between days 4-8 p.i. GITR also increases the ratio of T follicular helper to T follicular regulatory cells, thereby enhancing LCMV-specific IgG production. Together, these findings identify a CD4 T cell-intrinsic role for GITR in sustaining early CD8 and late humoral responses to collectively promote control of chronic LCMV clone 13 infection.
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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) | 0.001 | 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) | 0.003 | 0.001 |
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".