title: Immunophenotyping of peripheral immunoregulatory as well as Th17A and Th22 cell subpopulations in kidney transplant recipients under belatacept or cyclosporine treatment.
abstract: OBJECTIVE
  Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induce peripheral tolerance, while Th17A and Th22 cell subpopulations are of proinflammatory nature. The aims of the study were to characterize and to enumerate peripheral Tregs, Bregs, and DCregs and Th17A and Th22 cell subpopulations in kidney transplant recipients (KTRs) under belatacept or cyclosporine treatment.
  
  
  METHODS
  Forty-one KRT patients (30 under belatacept treatment and 11 under cyclosporine treatment) and 26 healthy donors (HDs) were included in the study. CD19(+)-expressing peripheral B lymphocytes were purified by positive selection. IL-10-producing B cells, CD4(+)/CD25(high)Foxp3(+), and CD8(+)/CD28(-)Foxp3(+) Tregs, CCR6(+)/CD123(+)/IDO(+) DCs, as well as Th17A and Th22 cell subpopulations were quantitated by flow cytometry.
  
  
  RESULTS
  Of the IL-10-producing Bregs, CD19(+)/CD24(high)/CD38(high)/CD5(+), CD19(+)/CD24(high)/CD38(high)/CD10(+), CD19(+)/CD24(high)/CD38(high)/CD20(+), and CD19(+)/CD24(high)/CD38(high)/CD27(-) had significant higher frequency in patients under belatacept treatment when compared with those under cyclosporine. Only CD19(+)/CD24(high)/CD38(high)/CD27(+) and CD19(+)/CD24(high)/CD38(high)/CXCR7(+) cells had significant higher frequency in patients under cycloporine treatment when compared to those under belatacept. The percentages of IDO-expressing pDC, CD4(+)/CD25(high)Foxp3(+), and CD8(+)/CD28(-)Foxp3(+) were significantly higher in the belatacept group when compared the cyclosporine one, while Th17A and Th22 cells had significant higher frequency in the latter group.
  
  
  CONCLUSIONS
  Belatacept seems to maintain and enhance, at least systemically, a tolerant profile to renal allograft in transplant recipients by means of higher circulatory frequencies of regulatory B, T and pDC subpopulations.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Janette
authors.initials: J
authors.lastname: Furuzawa-Carballeda
authors.affiliation: Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Bostock
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Lima
authors.affiliation: Transplantation, Instituto Nacional de Cardiología, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mancilla-Urrea
authors.affiliation: Instituto Mexicano de Trasplantes, Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mondragón
authors.affiliation: Transplantation, Hospital Miguel Hidalgo, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Reyes-Acevedo
authors.affiliation: Nephrology and Transplantation, Hospital Ignacio Morones Prieto, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Chevaile
authors.affiliation: Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Morales-Buenrostro
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Electronic address: luisllorentepeters57@gmail.com.
authors.forename: Luis
authors.initials: L
authors.lastname: Llorente
authors.affiliation: Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Electronic address: josefinaalberu@hotmail.com.
authors.forename: Josefina
authors.initials: J
authors.lastname: Alberú
mesh_terms: D000069594:Abatacept; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D003430:Cross-Sectional Studies; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D014181:Transplantation Immunology / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D016572:Cyclosporine
keywords: Belatacept; Cyclospirine; Kidney transplantation; Proinflammatory cells; Regulatory cells