CD8 T cells require intrinsic GITR signaling for their clonal expansion during influenza infection in vivo (50.21)
Bibliographic record
Abstract
Abstract Several members of the tumor necrosis factor receptor family regulate T cell expansion by influencing T cell activation and survival. Among these, glucocorticoid-induced TNF receptor family-related gene (GITR) is of interest, as it is expressed on both effector and regulatory T cells. While much work has focused on the role of GITR on regulatory T cells, little is known about its role on effector T cells in an infectious disease context. We sought, therefore, to examine the intrinsic role of GITR on CD8 T cells during a viral infection. To do this, we employed an adoptive transfer model where WT and GITR-/- TCR transgenic OT-I CD8 T cells were forced to compete with each other in response to infection with a recombinant influenza virus carrying the ovalbumin epitope recognized by OT-I, Influenza A/X31-OVA. In both the primary and secondary response to virus profound defects in GITR-/- OT-I T cell numbers were detected in all organs examined. Further investigation revealed that the decreased number of GITR-/- OT-I T cells was not due to a homing or proliferative defect, but rather that GITR was important for TRAF2 and TRAF5 mediated T cell survival signaling. Moreover, we also used a similar adoptive transfer model to show that GITR is required on CD8 T cells for enhancement of influenza-specific CD8 T cell expansion upon administration of agonistic anti-GITR antibody. These results highlight the importance of GITR as a CD8 T cell costimulator during acute viral 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) | 0.001 | 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".