INDUCTION OF BONE MARROW-DERIVED TOLERANCE-INDUCING APC USING MABS TO CD200R
Bibliographic record
Abstract
O39* Aims: CD200 is a relatively ubiquitously expressed type-1 transmembrane protein which we and others have reported is implicated in delivery of immunoregulatory signals following engagement of its receptor, CD200R. Expression of the latter is more restricted (predominantly to lymphoid and myeloid cells), though recent evidence from our own group and others suggest that a family of CD200Rs exist (our nomenclature: CD200R1-4), with different members showing restricted tissue specificity. To date little is known concerning the functional activity of CD200Rs expressed on cells in different tissues. Using isoform-specific anti-CD200R mAbs we have investigated the effect of inclusion of these mAbs on the generation of alloimmunity in MLR cultures, or on the generation of stimulatory dendritic cells (DCs) from bone marrow cells cultured in vitro in the presence of (IL-4 + GM-CSF). Methods: Primary MLR cultures were set up with 1:1 mixtures of C3H stimulator spleen cells, and mitomycin-c treated C57BL/6 stimulator cells. Some cultures contained the different anti-CD200R mAbs (5μg/ml). Cytokines were assayed in culture supernatants at 40hrs by ELISA, and CTL were assayed at day 5 (using 51Cr-labeled EL4 tumor target cells). In another assay using these anti-CD200R mAbs, bone marrow cells were cultured for 8 days with GMCSF and IL-4 in the presence/absence of mAbs, to generate DCs. DC maturation was induced by inclusion of LPS (1μg/ml) over the last 18hr of culture, and these mitomycin-c treated DCs were used to induce CTL and cytokine production after culture with C3H responder spleen cells. Results: Inclusion of anti-CD200R1 mAb (but not anti-CD200R2-4) to MLR cultures caused suppression of production of type-1 cytokines (IL-2, IFNγ), and of generation of CTL in vitro. In contrast, addition of anti-CD200R2/3 mAbs (but not anti-CD200R1) in bone marrow cultures led to generation of DCs which were unable to produce allostimulation in vitro with responder spleen cells. Instead, cells taken from these latter cultures contained a population of CD4+ CD25+ cells able to inhibit the antigen-specific MLR response of fresh C3H responder cells to stimulation with C57BL/6 cells, but not stimulation with BALB/c cells. In addition, these cells, infused in vivo into mice receiving C57BL/6 skin grafts, produced antigen-specific decreased rejection of BL/6 allografts, not BALB/c allografts, compared with mice receiving control cells (generated from bone marrow in the absence of anti-CD200R). The suppression induced in vitro using cells from the initial bone marrow cultures (derived in the presence of anti-CD200R2/3) could be overcome in secondary MLCs by using limiting numbers of these cells, and an excess of allostimulatory cells derived from bone marrow cultures maintained in the absence of anti-CD200R. Conclusions: Our data suggest that unlike anti-CD200R1, anti-CD200R2/3 biases stem cells in bone marrow towards development of suppressive antigen-presenting cells, which can be monitored in vitro and which have the potential to modify graft acceptance in vivo.
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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) | 0.001 | 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) | 0.002 | 0.001 |
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".