Transfer of Recipient MHC Proteins to Donor Cells (trogocytosis) During Xenograft Bone Marrow Transplantation
Notice bibliographique
Résumé
Abstract Abstract 4698 Background: Hematopoietic cell transplantation (HCT) is a common procedure for eradicating blood cancers and other diseases that involves reconstitution of the bone marrow and regeneration of the immune system after full or partial myeloablative therapy. Despite the widespread use of HCTs, no studies have investigated the extent of cell fusion or trogocytosis between blood cells of the donor and recipient in the transplant setting despite the many reports of fusion between blood cells and non-blood cells in the stem cell literature. The potential transfer of mismatched Class 1 MHC proteins and other surface molecules between cells by trogocytosis as identified in our study, has implications for outcome after allogeneic hematopoietic cell transplantation, specifically with reduced intensity conditioning regimens. A complete understanding of the cellular and molecular mechanisms of trogocytosis and its effect on the graft-versus–tumor effect, graft-versus-host disease (GVHD) and graft rejection will provide new insights that are likely to improve results of allotransplantation. Results: Using human donor HSCs to engraft NOD/SCID mice resulted in 100% of surviving donor cells with recipient (mouse) MHC class 1 on their surface in high concentrations. We also report on the transfer of CD45, CD56, CD14, CD41 and class 2 MHC proteins. Furthermore we could also demonstrate that radiation pre-conditioning increases the rate of trogocytosis between blood cells. Mouse chimeras were generated between MHC mismatched strains allowing us to investigate trogocytosis between blood cells in a none radiation setting as well as potential trogocytosis between blood cells and organs. Implications of this study: Trogocytosis has been described as a method of antigen presentation during a normal immune reaction. The paradox we have encountered and explore in our study is the fact that the trogocytosis we observe in the transplantation setting occurs in ‘reverse’ to what is expected. It is expected that during HCT the donor cells would be targeted for destruction by either recipient NK cells or T-cells. Even in the xenograft transplant model using NOD/SCID mice the residual NK cells are known to cause graft rejection. The literature regarding standard blood cell rejection indicates that the recipient NK, T cells and APCs acquire donor MHC through direct mechanisms (intact allo-MHC on APCs) or indirect mechanisms (processed donor (allo) antigen + self-MHC) resulting in the rejection of the donor cells. What we actually observe is the reverse. All donor cells acquire recipient MHC class 1. This novel observation of unidirectional transfer of MHC implies that trogocytosis could protect against graft rejection while not reducing graft-versus-tumor activity, thereby creating an opportunity for increasing patient survival rates. Despite the extensive use of experimental and clinical allotransplantation, fusion or trogocytosis between blood cells has not been well documented. Moreover, trogocytosis has not been considered in the stem cell field mainly because its mechanism is unknown and its significance has been limited to antigen presentation and to T-cells involved in immune reactions. Disclosures: Rogers: Insception Biosciences: Consultancy.
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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) | 0,000 | 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 | 0,000 |
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 ».