Control of human cytomegalovirus replication by liver resident natural killer cells
Bibliographic record
Abstract
Abstract Natural killer (NK) cells are innate immune cells that have been suggested important for control of human cytomegalovirus (HCMV) – an important pathogen in immune suppressed transplant patients. In HCMV seropositive individuals a population of NK cells with adaptive features can expand in peripheral blood and has been shown to have enhanced antiviral function. This is particularly evident following solid organ transplant (SOT) where patients frequently experience episodes of HCMV viremia. In contrast, much less is understood about the identity and function of tissue-resident immune cells in the context of HCMV infection and pathogenesis. In this study, access to tissue-resident immune cells from human organs destined for transplant has enabled us to address this, for the first time. Here we show that human liver-resident (lrNK), like circulating NK (cNK) cells, express increased adaptive markers in HCMV+ individuals. Interestingly, lrNK demonstrated better control of HCMV replication in vitro when compared to cNK cells isolated from the same donor. Furthermore, this control phenotype was elevated if the cells were isolated from HCMV seropositive donors. Crucially, because these studies were performed on perfusates from livers destined for transplantation we could correlate a donor’s lrNK ability to control HCMV in vitro with a reduction in HCMV viraemia in liver transplant recipients in vivo. Finally, we demonstrate that a population of CD2+ NK cells are enriched in patients who did not develop viraemia post-transplant and that loss of control in vitro occurs when CD2 NK cells are depleted or inhibited with anti-CD2 antibodies. Therefore, lrNK have anti-viral activity that could be important for control of HCMV replication in tissue and contribute to better clinical outcomes following organ transplant. Understanding the importance of CD2 expressing populations could have implications for the development of novel therapies aimed at mobilising specific NK cell functions against infections and/or decreasing the ability of HCMV to evade NK responses.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".