DIRECT ORCHESTRATION OF CD8+ T-KILLERS BY CD4+ T-HELPERS AND CD+ T-LICENSED ANTIGEN PRESENTING CELLS (130.33)
Bibliographic record
Abstract
Abstract We previously proposed a CD4+ Th-APC concept by demonstrating that in vitro ovalbumin (OVA)-pulsed dendritic cell (DCova)-activated CD4+ T cells acquired peptide/major histocompatibility complex (pMHC) I from DCova and are capable of stimulating CD8+ cytotoxic T lymphocytes (CTLs). In this study, we developed a novel immunization protocol to “dissect apart” respective roles of DCova, CD4+ and CD8+ T cells separately in an in vivo environment with close to physiological condition. We first used anti-CD4 and anti-CD8 antibody (Ab) and deptheria toxin (DT) for in vivo depletion of CD4+ and CD8+ T cells and DCova derived from DT receptor (DTR)-CD11c transgenic mice, respectively, at different time points of the protocol. We then assessed the priming of CD8+ CTL responses in blood using FITC-CD8 and PE-Kb/OVA257-264 tetramer staining by flow cytometry. We found that (i) mice that have CD4+ T-licensed DCova but lack CD4+ T cells by anti-CD4 Ab treatment during CD8+ CTL priming, induced CTL effector/memory responses, (ii) CD4+ T cells with in vivo acquired pMHC I, but not those without pMHC I acquisition stimulated CTL responses, and (iii) APC-primed CD4+ T cells mounted more efficient CTL effector/memory responses than CD4+ T-licensed DCova. Our results thus provide a clear in vivo evidence for a direct orchestration of CD8+ T-killers by CD4+ T-helpers and CD4+ T-licensed APCs. This conceptual advance may have great impacts in re-evaluation of antitumor and autoimmune 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) | 0.001 | 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".