title: Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine.
abstract: BACKGROUND
  Allergen-specific immunotherapy (SIT) faces problems related to side effects and limited efficacy. Direct administration of allergen extracts into lymph nodes induces increased specific IgG production and T-cell responses using significantly lower allergen doses.
  
  
  METHODS
  In this study, mechanisms of immune regulation by MAT vaccines in vitro and in allergen-SIT of cat-allergic rhinitis patients, who received 3 inguinal intra-lymph node injections of MAT-Fel d 1 vaccine, were investigated in PBMC and cell cultures for specific T-cell proliferation, Fel d 1-tetramer-specific responses, and multiple immune regulatory molecules.
  
  
  RESULTS
  MAT-Fel d 1 vaccine was efficiently internalized by antigen-presenting cells. This was followed by precaspase 1 cleavage to caspase 1 and secretion of IL-1β, indicating inflammasome activation. Mat-Fel d 1 induced specific T-cell proliferation and an IL-10- and IFN-γ-dominated T-cell responses with decreased Th2 cytokines at 100 times lower doses than Fel d 1. Induction of immune tolerance by MAT-Fel d 1-ILIT involved multiple mechanisms of immune suppression. Early Fel d 1-specific T-cell activation was followed by full T-cell unresponsiveness to allergen after 1 year in the MAT-Fel d 1 group, characterized by increased allergen-specific T regulatory cells, decreased circulating Fel d 1 tetramer-positive cells, increased IL-10 and FOXP3 expression, and change in the HR2/HR1 ratio toward HR2.
  
  
  CONCLUSIONS
  This study demonstrates the induction of allergen tolerance after 3 intra-lymph node injections of MAT-Fel d 1 vaccine, mediated by increased cellular internalization of the allergen, activation of inflammasome, and generation of allergen-specific peripheral T-cell tolerance.
authors.affiliation: Swiss Institute for Allergy and Asthma Research (SIAF), Davos, Switzerland; Department and Clinic of Internal Diseases, Geriatry and Allergology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Zaleska
authors.forename: T
authors.initials: T
authors.lastname: Eiwegger
authors.forename: O
authors.initials: O
authors.lastname: Soyer
authors.forename: W
authors.initials: W
authors.lastname: van de Veen
authors.forename: C
authors.initials: C
authors.lastname: Rhyner
authors.forename: M B
authors.initials: MB
authors.lastname: Soyka
authors.forename: C
authors.initials: C
authors.lastname: Bekpen
authors.forename: D
authors.initials: D
authors.lastname: Demiröz
authors.forename: A
authors.initials: A
authors.lastname: Treis
authors.forename: S
authors.initials: S
authors.lastname: Söllner
authors.forename: O
authors.initials: O
authors.lastname: Palomares
authors.forename: W W
authors.initials: WW
authors.lastname: Kwok
authors.forename: H
authors.initials: H
authors.lastname: Rose
authors.forename: G
authors.initials: G
authors.lastname: Senti
authors.forename: T M
authors.initials: TM
authors.lastname: Kündig
authors.forename: N
authors.initials: N
authors.lastname: Ozoren
authors.forename: M
authors.initials: M
authors.lastname: Jutel
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
authors.forename: R
authors.initials: R
authors.lastname: Crameri
authors.forename: M
authors.initials: M
authors.lastname: Akdis
mesh_terms: D015153:Blotting, Western; D003888:Desensitization, Immunologic / Q000379:methods*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D006023:Glycoproteins; D014612:Vaccines; C059296:Fel d 1 protein, Felis domesticus
keywords: cat allergy; intralymphatic immunotherapy; modular allergen translocation; rFel d 1; tetramer