title: Coating human pancreatic islets with CD4(+)CD25(high)CD127(-) regulatory T cells as a novel approach for the local immunoprotection.
abstract: OBJECTIVE
  To develop a novel approach for local immunoprotection using CD4(+)CD25(high)CD127(-) T regulatory cells (Tregs) attached to the surface of the islets before transplantation.
  
  
  BACKGROUND
  Tregs expanded ex vivo can control allo and autoreactivity, therefore, Treg-based therapy may offer more effective protection for transplanted islets from immunologic attack than currently used immunosuppression. Local application of Tregs can make such therapy more clinically feasible and efficient.
  
  
  METHODS
  Human islets were isolated and coated with allogeneic ex vivo expanded Tregs using biotin-poly(ethylene glycol)-N-hydroxysuccinimide ester (biotin-PEG-NHS) and streptavidin as binding molecules.
  
  
  RESULTS
  Coating pancreatic islets with Tregs did not affect islet viability (>90% fluorescein diacetate/propidium iodide) or the insulin secretion profile in dynamic islet perifusion assays. After in vitro incubation with allogeneic T effector cells, Treg-coated islets revealed preserved function with higher insulin secretion compared with controls-native islets, coated islets with T effector cells or when Tregs were added to the culture, but not attached to islets (P < 0.05). In addition, the Enzyme-linked immunosorbent spot (ELISPOT) assay revealed suppression of interferon (IFN)-γ secretion, when T effector cells were challenged with Treg-coated islets comparing to controls (99 ± 7 vs 151 ± 8 dots, respectively; P < 0.01).
  
  
  CONCLUSIONS
  We demonstrated, for the first time, the ability to bind immune regulatory cells to target cells with preservation of their viability and function and protective activity against immune attack. If successfully tested in an animal model, local delivery of immunoprotective Tregs on the surface of transplanted pancreatic islets may be an alternative or improvement to the currently used immunosuppression.
authors.affiliation: Department of Surgery, Section of Transplantation, University of Chicago, IL 60637, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Marek
authors.forename: Adam
authors.initials: A
authors.lastname: Krzystyniak
authors.forename: Ipek
authors.initials: I
authors.lastname: Ergenc
authors.forename: Olivia
authors.initials: O
authors.lastname: Cochet
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Misawa
authors.forename: Ling-Jia
authors.initials: LJ
authors.lastname: Wang
authors.forename: Karolina
authors.initials: K
authors.lastname: Gołąb
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.forename: German
authors.initials: G
authors.lastname: Kilimnik
authors.forename: Manami
authors.initials: M
authors.lastname: Hara
authors.forename: Seda
authors.initials: S
authors.lastname: Kizilel
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.forename: J Michael
authors.initials: JM
authors.lastname: Millis
authors.forename: Piotr
authors.initials: P
authors.lastname: Witkowski
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005240:Feasibility Studies; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D007371:Interferon-gamma