Cognate CD4+ T cells enhance CTL survival and memory programming via IL-2, CD40L and acquired pMHC-I signaling (46.16)
Bibliographic record
Abstract
Abstract A hallmark of cellular immunity is the generation of memory CD8+ cytotoxic T lymphocytes (CTL) that escape activation-induced cell death (AICD) during the effector phase. Factors governing effector CTL survival in CD4+ T helper1 cells (Th1) that lead to functional memories are poorly understood. Here, we determined the role of Th1 cells with acquired antigen-presenting machineries on effector CTL fates. Contrary to previously known immune-regulatory mechanisms among Th1 or CTL interactions, our study establishes a novel co-operative role of cognate Th1-CTL interactions. Th1’s help mediated enhanced CTL survival, and functional memory CTL development, capable of protecting against lethal tumor challenge, via CD40L, IL-2, and acquired peptide-MHC-I signaling. Helped CTL showed survival advantages by displaying mRNA profiles similar to naïve CD8+ T cells, and increased NF-kB and Akt1 activation. In contrast, unhelped CTL underwent rapid AICD-mediated contraction through increased NFATc1 activation, and up-regulation of pro-apoptotic and down-regulation of anti-apoptotic genes known to mediate FasL- and Trail-associated apoptotic pathways. This form of Th1-CTL cooperation could explain why memory CTL generated under cognate Th1’s help show survival and recall advantages, a phenomenon frequently observed in organ transplantations, cancers, and many autoimmune and infectious diseases, and may impact effective adoptive CTL therapy of cancers.
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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) | 0.002 | 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".