title: Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.
abstract: BACKGROUND
  Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI.
  
  
  METHODS
  In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture.
  
  
  RESULTS
  The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality.
  
  
  CONCLUSIONS
  Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.
authors.affiliation: 1 Multi-Organ Transplant Program, McGill University Health Centre, McGill University, Montreal, QC, Canada. 2 Division of General Surgery, Department of Surgery, McGill University Health Centre, McGill University, Montreal, QC, Canada. 3 Division of Nephrology, Department of Medicine, McGill University Health Centre, McGill University, Montreal, QC, Canada. 4 Division of Nephrology, Department of Medicine, Jewish General Hospital, McGill University, Montreal, QC, Canada.
authors.forename: Minh-Tri J P
authors.initials: MT
authors.lastname: Nguyen
authors.forename: Elise
authors.initials: E
authors.lastname: Fryml
authors.forename: Sossy K
authors.initials: SK
authors.lastname: Sahakian
authors.forename: Shuqing
authors.initials: S
authors.lastname: Liu
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
authors.forename: Mark
authors.initials: M
authors.lastname: Lipman
authors.forename: Jean I
authors.initials: JI
authors.lastname: Tchervenkov
authors.forename: Steven
authors.initials: S
authors.lastname: Paraskevas
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D018920:Coculture Techniques; D051799:Delayed Graft Function / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood / Q000276:immunology*; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000276:immunology*; D006435:Renal Dialysis; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D053699:Interleukin-7 Receptor alpha Subunit; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human