Human cytomegalovirus IL-10 augments NK cell cytotoxicity
Bibliographic record
Abstract
Human cytomegalovirus (HCMV) persistently infects most of the adult population with periods of productive and latent infection differentially orchestrated by multiple HCMV-encoded gene products. One HCMV gene (UL111a) encodes cmvIL-10, a virokine homologous to human IL (hIL)-10. Although the effects of cmvIL-10 on most human lymphocyte subsets have been extensively studied, its impact on NK cell function was unreported prior to this study. We investigated effects of short-term cmvIL-10 exposure on human NK cells and found it substantially enhanced NK cell cytotoxicity through natural cytotoxicity receptors NKp30 and NKp46 as well as through C-type lectin-like receptors NKG2C and NKG2D. Antibody-dependent cell-mediated cytotoxicity triggered through CD16 also increased significantly with short-term cmvIL-10 exposure. These effects of cmvIL-10 on NK cell cytotoxicity were rapid, dose dependent, neutralized by polyclonal anti-cmvIL-10 or monoclonal anti-IL-10 receptor (IL-10R) antibodies and independent of increased perforin synthesis or up-regulation of activating receptors. A low percentage (0.5-5.4%; n = 12) of NK cells expressed IL-10R and the impact of cmvIL-10 on NK cells degranulation following CD16 stimulation directly correlated with this percentage (P = 0.0218). Short-term exposure of human NK cells to cmvIL-10 did not introduce phenotypic changes reminiscent of NK adaptation to HCMV infection in vivo. Determining how expression of a viral protein that activates NK cells contributes to their function in vivo will increase understanding of HCMV infection and NK cell biology.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.012 | 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".