INDUCTION OF BONE MARROW-DERIVED TOLERANCE-INDUCING APC USING MABS TO CD200R
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».