Dynamic regulation correlates with variable inhibitory function of CD244 on antiviral CD8 T cells (P6117)
Bibliographic record
Abstract
Abstract Antigen-experienced T cells express a wide variety of costimulatory molecules, some of which can contribute to activating, inhibitory, or exhaustion pathways depending on context. In particular 2B4 (CD244/ SLAMf4) has been shown to be capable of either inhibitory or enhancing effects upon engagement of its ligand CD48 (SLAMf2). We examined the phenotypes of CD8 T cell lines and clones derived from HIV-infected or -uninfected subjects, and specific for HIV or for respiratory syncytial virus. Antiviral CTL expressed varying levels of PD-1, 2B4, and TIM-3. Cognate peptide induced rapid downregulation of both 2B4 and TIM-3, but not PD-1 on cultured CD8 T cells. 2B4 downregulation also occurred directly ex vivo and required simultaneous signaling via both TCR and 2B4, as downregulation was not observed in the absence of antigen or in the presence of CD48-blocking antibody. 2B4 downregulation was not induced by PMA or prevented by PI3-kinase inhibition, implicating a TCR-proximal signaling mechanism. Downregulation occurred rapidly upon stimulation with a low dose of peptide, concomitant with internalization of CD3 and CD8. The degree of 2B4 downregulation varied among CD8 T cells of different specificities and HLA restrictions, and the degree of downregulation correlated with the respective enhancement or suppression of antiviral IFNγ production in response to CD48 blockade. Our results indicate a role for 2B4 downregulation in modulation of antiviral CD8 T cell responses.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".