P01-05. Rapid perforin upregulation dominates the HIV-specific CD8 T cell response during acute HIV-infection
Bibliographic record
Abstract
Recent dogma suggests that CD8 T cell ''polyfunctionality'' is essential for control of HIV, however none of the commonly measured functions are likely responsible for clearing infected target cells. During acute HIV infection, when HIV-specific CD8 T cells are thought to resolve peak viremia, an effector response has not been formally demonstrated. PBMC from 23 acutely infected HIV patients were stimulated with pools of overlapping peptides encompassing all HIV open reading frames. A panel of antibodies directed against cell surface and intracellular entities was employed to stain for HIV-specific CD8 T cells by flow cytometry. Functionality was assessed by the ability to upregulate perforin, IFN-γ, IL-2, TNF-α, MIP-1β, and CD107a simultaneously. Nineteen of 23 (82.6%) subjects mounted an HIV-specific CD8 T cell response of at least 3 functions against a minimum 1 peptide pool, however none of the cells were capable of performing all functions. While MIP-1β and CD107a were ubiquitous functions, and TNF-α and IFN-γ were consistently expressed, IL-2 production was rarely observed. In contrast, the majority of subjects (17/19; 89.5%) demonstrated a pronounced ability to upregulate perforin upon HIV-specific stimulation. Even in the absence of highly polyfunctional responses perforin upregulation was reliably detected; 16/17 (94.1%) perforin responders displayed a strong perforin+degranulation+ subset. The HIV-specific CD8 T cells capable of perforin upregulation were largely effector (CCR7-CD45RO-) or effector memory (CCR7-CD45RO+), and most of these cells co-expressed CD57. Rather than the absolute number of functions an HIV-specific CD8 T cell can perform, it is the quality of the functions that correlates to potential control HIV replication. Being that rapid perforin upregulation is a direct marker of in vivo cytotoxicity, its prevalence during acute HIV infection, even in concert with only degranulation, provides compelling evidence for a critical role of CD8 T cells in the control of acute HIV infection.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 | 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 | 0.006 |
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; both teacher heads agree on what is shown here.
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".