title: Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice.
abstract: BACKGROUND
  Recently, we developed a humanized mouse model of allergen-induced IgE-dependent gut inflammation in PBMC-engrafted immunodeficient mice.
  
  
  OBJECTIVE
  In the present study, we wanted to investigate the role of regulatory T (Treg) cells and their activation status in this model.
  
  
  METHODS
  Nonobese diabetic-severe combined immunodeficiency-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or NaCl as control in the presence or absence of different concentrations of CD4(+)CD25(+) Treg cells of the same donor. After an additional allergen boost 1 week later, mice were challenged with the allergen rectally on day 21 and gut inflammation was monitored by a high-resolution video mini-endoscopic system evaluating translucency, granularity, fibrin production, vascularity, and stool.
  
  
  RESULTS
  Allergen-specific human IgE in mouse sera, which was detectable only in PBMC plus allergen-treated mice, was strongly inhibited by coinjection of Treg cells at a ratio of at least 1:10. Consequently, the presence of Treg cells significantly decreased IgE-dependent allergen-induced gut inflammation after rectal allergen challenge. In addition, Treg cells reduced allergen-specific proliferation and cytokine production of recovered human CD4(+) T cells in vitro. Activation of Treg cells before injection further increased all inhibitory effects. Prevention of gut inflammation also occurred by the administration of glycoprotein A repetitions predominant, a molecule expressed by activated Treg cells, whereas its blockade completely abrogated inhibition by Treg cells.
  
  
  CONCLUSIONS
  These results demonstrate that allergen-specific gut inflammation in human PBMC-engrafted mice can be avoided by enhancing the numbers or activity of autologous Treg cells, which is of great interest for therapeutic intervention of allergic diseases of the intestine.
authors.affiliation: Department of Dermatology, University Hospital Erlangen, University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Eschborn
authors.affiliation: Department of Internal Medicine I, University Hospital Erlangen, University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Weigmann
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Reissig
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.affiliation: Department of Dermatology, University Hospital Erlangen, University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Saloga
authors.affiliation: Department of Dermatology, University Hospital Erlangen, University Erlangen-Nürnberg, Erlangen, Germany. Electronic address: iris.bellinghausen@unimedizin-mainz.de.
authors.forename: Iris
authors.initials: I
authors.lastname: Bellinghausen
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000637:transplantation; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; C087215:LRRC32 protein, human; D008565:Membrane Proteins; D007073:Immunoglobulin E
keywords: Humanized mice; IgE; allergen; colon; inflammation; regulatory T cells