S03-06 OA. Rapid perforin upregulation by CD8 T cells in elite controllers as a correlate of immune-mediated control of HIV replication
Bibliographic record
Abstract
Evidence suggests that CD8 T cells are important to the control of HIV replication in elite controllers. However, the mechanism behind the enhanced suppressive capacity of CD8 T cells in these subjects remains unclear. We have recently discovered the novel ability of human CD8 T cells to rapidly upregulate perforin following antigen-specific stimulation. Using polychromatic flow cytometry and standard intracellular cytokine staining assays, we measured perforin expression, cytokine production, and degranulation by CD8 T cells following stimulation using overlapping peptide pools encompassing the entire HIV proteome. We studied several HIV-infected groups that differentially control viral replication off therapy: elite controllers (n = 34), viremic controllers (n = 29), chronic progressors (n = 24), and viremic nonprogressors (n = 6). We observe that on average 40% of the total CD8 T cell response in elite controllers is perforin-positive following HIV-specific stimulation compared to 20% in the other cohorts. However, the proportion of the HIV-specific CD8 T cell response that produces IFN-gamma does not vary widely between the groups. Elite controllers have a significantly larger proportion of responding CD8 T cells that degranulate yet remain perforin-positive following 6 hours of stimulation, suggesting that CD8 T cells in these individuals have an increased capacity to upregulate new perforin production. The cells that express perforin, which are enriched in elite controllers, display almost entirely an effector phenotype (CD27negCD45ROnegCD57+/-). Overall, there is a strong negative correlation (p < 0.0001) between HIV-specific perforin expression and viral load. This finding is not simply the result of the low viral load in elite controllers as HIV-specific perforin expression is not restored in HAART-suppressed patients (n = 12). The rapid perforin upregulation displayed by CD8 T cells in elite controllers may contribute to the superior control of HIV replication in these subjects. Continuous perforin expression following initial antigen encounter allows for the sustained cytotoxic potential of anti-viral CD8 T cells.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.026 | 0.004 |
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".