title: High levels of IDO-expressing CD16+ peripheral cells, and Tregs in graft biopsies from kidney transplant recipients under belatacept treatment.
abstract: BACKGROUND
  Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that suppresses T-lymphocyte activity. Costimulation blockade through CTLA4lg increases IDO in antigen-presenting cells. The suppressive effect of IDO is thought to be mediated by Foxp3+CD4+CD25+ regulatory T-cells (Tregs).
  
  
  OBJECTIVE
  In this descriptive study, we evaluated the percentage of IDO-expressing peripheral cell subpopulations as well as Tregs in 27 stable kidney transplant recipients receiving either belatacept (LEA29Y), a daughter compound of abatacept (CTLA4lg; n = 19) or cyclosporine (n = 8).
  
  
  METHODS
  Blood samples were obtained at 24 ± 2 months (belatacept) and 23 ± 6 months (cyclosporine) of treatment. Intracellular IDO was analyzed by flow cytometry in CD14+, CD11c+, CD16+, CD56+, and CD8+ cell subpopulations. Tregs were assessed by intracellular Foxp3 detection in CD4+CD25+ cells. CD3+, CD4+, CD8+, CD20+, CD68+, IDO+, and Foxp3+ cells were evaluated by immunohistochemistry on graft biopsies obtained preimplantation, at 12 months posttransplant, and in subjects with dysfunction during the first 12 months.
  
  
  RESULTS
  Only percentages of CD16+/IDO+-expressing peripheral monocytes were significantly increased among the group receiving belatacept. No differences were observed in peripheral Tregs between the groups. In contrast, higher percentages of Tregs, CD4+, CD8+, and CD68+ cells were noted in dysfunction and at 12 months vs baseline among graft biopsies in subjects receiving belatacept, and also among dysfunction cohorts of belatacept vs Cyclosporine treatment.
  
  
  CONCLUSIONS
  Patients receiving belatacept showed greater amounts of peripheral blood CD16+/IDO+ cells and Tregs on graft biopsies than those under cyclosporine treatment.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Furuzawa-Carballeda
authors.forename: G
authors.initials: G
authors.lastname: Lima
authors.forename: N
authors.initials: N
authors.lastname: Uribe-Uribe
authors.forename: C
authors.initials: C
authors.lastname: Avila-Casado
authors.forename: E
authors.initials: E
authors.lastname: Mancilla
authors.forename: L E
authors.initials: LE
authors.lastname: Morales-Buenrostro
authors.forename: J
authors.initials: J
authors.lastname: Pérez-Garrido
authors.forename: M
authors.initials: M
authors.lastname: Pérez
authors.forename: G
authors.initials: G
authors.lastname: Cárdenas
authors.forename: L
authors.initials: L
authors.lastname: Llorente
authors.forename: J
authors.initials: J
authors.lastname: Alberú
mesh_terms: D000069594:Abatacept; D000328:Adult; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D001706:Biopsy; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000097:blood*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C428200:FCGR3B protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D058851:GPI-Linked Proteins; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017452:Receptors, IgG; D000069594:Abatacept; D016572:Cyclosporine