A staphylococcal superantigen unexpectedly augments the response magnitude of cognate anti-influenza CD8+ T cells in mice and humans.
Bibliographic record
Abstract
Abstract Staphylococcal enterotoxin B (SEB) is a bacterial superantigen (SAg) that induces proliferation and inflammatory cytokine secretion by up to 30% of T cells present in one’s repertoire. Eventually, the exposed T cells are thought to undergo activation-induced cell death or anergy, thus creating physical and/or functional holes in the repertoire. Using a mouse model of influenza A virus (IAV) vaccination, we found that primary IAV-specific CD8+ T cell (TCD8+) responses were enhanced, rather than diminished, in SEB-exposed animals. This effect was manifest for both local and systemic responses and validated when several different strains of IAV were utilized. Strikingly, the observed enhancement was easily detectable even one month post-SEB exposure, which was much later than the peak of the anti-IAV response. Importantly, IAV-specific TCD8+ in SEB-primed animals were not only capable of synthesizing interferon (IFN)-γ but also of lysing target cells pulsed with IAV-derived peptides in vivo. Finally, in vitro cultures of human peripheral blood mononuclear cells with SEB revealed that memory TCD8+, which recognize IAV but not Epstein-Barr virus or cytomegalovirus, were specifically expanded by this SAg and persisted long after deletion should have theoretically occurred. Taken together, our findings define a novel phenomenon in the context of TCD8+ responses to SAgs, which has important implications for vaccination against flu in critical care patients afflicted by staphylococcal infections and/or SAg-mediated illnesses.
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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 | 0.002 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".