The anti-idiotypic antibody 1F7 stimulates monocyte interleukin-10 production and induces endotoxin tolerance
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: Pathogens that establish chronic infection elicit immune responses with suppressive cytokines dominating over pro-inflammatory cytokines. Chronic hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) infection and simian immunodeficiency virus (SIV) infection are associated with high levels of antiviral antibodies expressing a common idiotype specifically recognized by the 1F7 monoclonal antibody (mAb). The 1F7 mAb is a murine IgMκ antibody raised against immunoglobulin pooled from the plasma of multiple HIV-infected individuals. In this study, we investigated direct effects of the 1F7 mAb itself on peripheral blood mononuclear cells (PBMC). METHODS: Isolated monocytes or PBMC from healthy controls were incubated with the 1F7 mAb or IgMκ mAb control. Cytokine production was measured in cell culture supernatants by ELISA and cells producing interleukin-10 (IL-10) were identified by subset depletion and intracellular flow cytometry. Endotoxin tolerance was assessed by exposing monocytes to lipopolysaccharide (LPS) following 1F7 mAb or IgMκ mAb control pre-treatment and comparing tumor necrosis factor (TNF)-α levels in cell culture supernatants. RESULTS: The 1F7 mAb stimulated monocytes and CD36+ lymphocytes to produce IL-10 in a time and dose-dependent manner. Treatment of monocytes with 1F7 mAb also reduced their subsequent responsiveness to LPS stimulation. CONCLUSIONS: Induction of antibodies expressing the 1F7 idiotype by chronic pathogens may facilitate IL-10 production and progression to chronic infection. Direct effects of IL-10 from human monocytes stimulated by 1F7-like antibodies, followed by monocyte transition to an alternatively activated phenotype illustrated by endotoxin tolerance, are two complementary features favouring a tolerogenic or non-responsive immunological environment.
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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 | 0.001 |
| 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it