Inhibition of the CD8 T cell response and cytotoxicity by human intravenous immunoglobulin. (P5023)
Bibliographic record
Abstract
Abstract Intravenous immunoglobulin (IVIg) is made of plasma-derived human IgG and exerts anti-inflammatory effects in several autoimmune disorders when administered at high doses. The constant increase in its use exposes providers and patients to considerable risks of shortage. Understanding its complex mechanisms of action is required in order to develop potent substitutes. Our group previously demonstrated that IVIg inhibits the in vitro and in vivo activation of CD4 T cells (Aubin et al, Blood 2010), as well as the in vitro CD8 T cell activation (Trépanier et al, Blood 2012). In the present work, we investigated whether IVIg could also interfere with the CD8 T cell response, which contribute to the persistence and severity of many autoimmune conditions. Bone marrow-derived DC from C57BL/6 mice were treated with IVIg and used to cross-present ovalbumin to OVA-specific OT-I CD8 T cells. Proliferation and cytokine production were measured after 72 hours. Cytotoxicity was measured using SIINFEKL-pulsed EL-4 target cells in presence of therapeutic doses of IVIg. Results showed a reduced (50%) CD8 T cells activation in the presence of IVIg and a concomitant decrease in IL-2 and IFN-gamma secretion. In addition, IVIg-treated CD8 T cells are less cytotoxic, as measured by specific lysis of target cells. These results support a novel immunomodulatory mechanism by which IVIg decrease CD8 T cell response. The importance of these results in vivo are currently being investigated.
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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 | 0.001 |
| 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".