Pre-Operative Regulatory T Cell Suppressive Function Correlates with Short-Term Graft Outcome after Kidney Transplantation
Notice bibliographique
Résumé
Introduction: Regulatory T cells (Treg) are involved in preventing rejection and inducing tolerance after kidney transplantation by suppressing the action of effector T cells (Teff). A higher Treg frequency and suppressive function or a lower Teff frequency and proliferation prior to kidney transplantation could limit initial immunologic injury and be associated with better graft outcome post-transplant. We investigated whether Treg frequency and function or Teff frequency and proliferation correlated with estimated glomerular filtration rate (eGFR) following kidney transplantation. Methods: Peripheral blood was collected from 49 de novo kidney transplant recipients (44 deceased donors, 5 living donors) pre-operatively prior to induction immunosuppression (34 anti-thymocyte globulin, 12 alemtuzumab, 3 basiliximab). All recipients received tacrolimus and mycophenolate mofetil for maintenance immunosuppression, with corticosteroids used in all but the alemtuzumab group. Mononuclear cells were isolated by density centrifugation. CD4+CD25hiFoxP3+ Treg and CD4+CD25- Teff frequencies were measured by flow cytometry. For assessment of Treg suppressive function and Teff proliferation, CD4+CD25+ Treg (purity: 89 ± 1%) and CD4+CD25- Teff (purity: 85 ± 2%) were magnetically isolated. CFSE-labelled Teff were co-cultured in the presence of anti-CD3/CD28-coated beads with Treg at a 1:0 and 1:1 ratio for 5 days. Treg suppressive function was measured by percentage suppression of CFSE-labelled Teff proliferation. Graft function at 7, 14, 30, 90, and 180 days post-transplant was assessed by eGFR calculated by the MDRD formula. Correlations were made using Spearman's rank order correlation. Results: Pre-operative Treg frequency did not correlate with post-transplant eGFR. However, significant positive correlations were found between pre-operative Treg suppressive function and eGFR on post-transplant day 7, 14, 30, 90, and 180 (Fig 1A–E). Significant inverse correlations were also found between pre-operative Teff frequency and eGFR on post-transplant day 7, 14, and 30 (rs=-0.44 p< 0.01, rs=-0.35 p=0.02, and rs=-0.36 p=0.02 respectively). There were no correlations between pre-operative Teff proliferation and eGFR.[Figure 1]Conclusion: Pre-operative Treg suppressive function but not frequency correlated with graft function up to 180 days after kidney transplantation, while a weaker inverse correlation existed between pre-operative Teff frequency and graft function up to 30 days after transplantation. These results suggest that pre-operative Treg suppressive function measurement could be a tool to identify patients at risk for short-term graft dysfunction. Additionally, development of clinical strategies to enhance Treg suppressive function pre-emptively could improve outcomes in kidney transplantation.
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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 | 0,001 |
| 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 | 0,001 | 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) | 0,003 | 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 ».