The Early Induction of PDL1 On Monocytes by Ivig Suppresses T Cell Activation in Allogeneic Mixed Lymphocyte Reactions
Notice bibliographique
Résumé
Abstract Abstract 4111 Background: Recognition of histocompatibility determinants by allogeneic T cells together with the engagement of co-stimulatory molecules with their ligands expressed on accessory cells (B7:CD28, CD40:CD40L) is essential for the induction of T cell-mediated allograft rejection. In contrast, the PD1:PDL1 negative co-stimulatory pathway plays a critical role in the induction and maintenance of peripheral transplantation tolerance. Despite the use of potent immunosuppressive therapy for the blockade of co-stimulatory pathways, allograft rejection and drug toxicity remain an important problem in transplanted patients. IVIg was first used as a prophylactic agent in these immunocompromised patients to prevent infections, but several studies have suggested that IVIg also improved the rate of graft survival in patients with high risk for rejection. The mechanisms responsible for this anti-inflammatory effect are unclear and remain to be determined. We recently showed, using the allogeneic mixed lymphocyte reaction (MLR) as an in vitro model of allograft rejection and GvHD, that IVIg strongly inhibited T cell activation. In the present study, we sought to determine the mechanisms underlying this inhibition. Methods: For allogeneic MLR, human peripheral blood mononuclear cells (PBMC) from 2 different individuals were mixed together with or without 2 mg/ml of IVIg and incubated for 4 days prior to determination of IL-2 secretion by ELISA as a measure of T cell activation. The expression of TCR, CD3, CD28 and PD1 on T cells and HLA-DR, CD80, CD86 and PDL1 on monocytes was evaluated by flow cytometry. Results: IVIg strongly inhibited IL-2 secretion (>90%; P<0.001) as previously reported. To explain the inhibition of T cell activation in the presence of IVIg, we postulated that the expression of molecules involved in antigen presentation and in different co-stimulatory pathways was modulated by IVIg. We thus evaluated the effect of IVIg on the cell surface expression of various molecules implicated in T cell activation or tolerance, 24 hours after the onset of the MLR. Our results showed no modulation of TCR, CD3, CD28 and PD1 expression on T cells. Similarly, IVIg did not affect the expression of CD86 on monocytes. In contrast, the expression of CD80 was significantly decreased (>30%; P<0.01) on these cells after IVIg treatment. In addition, a strong increase in PDL1 expression (>70%; P<0.05) on monocytes was observed in MLRs done in the presence of IVIg. Finally, the expression of HLA-DR was increased by >60% (P<0.01) and that of CD14 was decreased by >50% (P<0.01) in the presence of IVIg, which is characteristic of the emergence of an anti-inflammatory monocyte population. Conclusion: Altogether, our results suggest that IVIg induces its immunosuppressive effects in allogeneic MLRs by modulating the expression of co-stimulatory molecules on monocytes and by inducing an anti-inflammatory monocyte population. This study contributes to a better understanding of the mechanisms by which IVIg may induce peripheral tolerance and improve graft survival in transplanted patients. Disclosures: No relevant conflicts of interest to declare.
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) | 0,001 | 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 ».