title: Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity.
abstract: BACKGROUND
  T-cell tolerance of allergic cutaneous contact sensitivity (CS) induced in mice by high doses of reactive hapten is mediated by suppressor cells that release antigen-specific suppressive nanovesicles.
  
  
  OBJECTIVE
  We sought to determine the mechanism or mechanisms of immune suppression mediated by the nanovesicles.
  
  
  METHODS
  T-cell tolerance was induced by means of intravenous injection of hapten conjugated to self-antigens of syngeneic erythrocytes and subsequent contact immunization with the same hapten. Lymph node and spleen cells from tolerized or control donors were harvested and cultured to produce a supernatant containing suppressive nanovesicles that were isolated from the tolerized mice for testing in active and adoptive cell-transfer models of CS.
  
  
  RESULTS
  Tolerance was shown due to exosome-like nanovesicles in the supernatants of CD8(+) suppressor T cells that were not regulatory T cells. Antigen specificity of the suppressive nanovesicles was conferred by a surface coat of antibody light chains or possibly whole antibody, allowing targeted delivery of selected inhibitory microRNA (miRNA)-150 to CS effector T cells. Nanovesicles also inhibited CS in actively sensitized mice after systemic injection at the peak of the responses. The role of antibody and miRNA-150 was established by tolerizing either panimmunoglobulin-deficient JH(-/-) or miRNA-150(-/-) mice that produced nonsuppressive nanovesicles. These nanovesicles could be made suppressive by adding antigen-specific antibody light chains or miRNA-150, respectively.
  
  
  CONCLUSIONS
  This is the first example of T-cell regulation through systemic transit of exosome-like nanovesicles delivering a chosen inhibitory miRNA to target effector T cells in an antigen-specific manner by a surface coating of antibody light chains.
authors.affiliation: Department of Immunology, Jagiellonian University College of Medicine, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bryniarski
authors.forename: Wlodzimierz
authors.initials: W
authors.lastname: Ptak
authors.forename: Asha
authors.initials: A
authors.lastname: Jayakumar
authors.forename: Kerstin
authors.initials: K
authors.lastname: Püllmann
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
authors.forename: Arthit
authors.initials: A
authors.lastname: Chairoungdua
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Adams
authors.forename: Emilia
authors.initials: E
authors.lastname: Sikora
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nazimek
authors.forename: Susanna
authors.initials: S
authors.lastname: Marquez
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.forename: Panjamaporn
authors.initials: P
authors.lastname: Sangwung
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Iwakiri
authors.forename: Eric
authors.initials: E
authors.lastname: Delgato
authors.forename: Frank
authors.initials: F
authors.lastname: Redegeld
authors.forename: Bart R
authors.initials: BR
authors.lastname: Blokhuis
authors.forename: Jacek
authors.initials: J
authors.lastname: Wojcikowski
authors.forename: Anna Wladyslawa
authors.initials: AW
authors.lastname: Daniel
authors.forename: Tom
authors.initials: T
authors.lastname: Groot Kormelink
authors.forename: Philip W
authors.initials: PW
authors.lastname: Askenase
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003877:Dermatitis, Contact / Q000517:prevention & control*; D000939:Epitopes; D055354:Exosomes / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D014176:Protein Biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000906:Antibodies; D000939:Epitopes; D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse