title: Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease.
abstract: BACKGROUND
  Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement.
  
  
  METHODS
  We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production.
  
  
  RESULTS
  We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-γ and TNF-α, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-γ and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines.Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas-Fas Ligand-mediated pro-apoptotic activity.
  
  
  CONCLUSIONS
  Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin- and Fas-Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-α, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF-α agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence Department of Surgery and Translational Medicine Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena SOD Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases -Behçet Center and Lupus Clinic - AOU Careggi Rheumatology and Clinical Immunology, Humanitas Research Hospital BIOMETRA Department, University of Milan, Milan, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Emmi
authors.forename: Elena
authors.initials: E
authors.lastname: Silvestri
authors.forename: Chiara Della
authors.initials: CD
authors.lastname: Bella
authors.forename: Alessia
authors.initials: A
authors.lastname: Grassi
authors.forename: Marisa
authors.initials: M
authors.lastname: Benagiano
authors.forename: Fabio
authors.initials: F
authors.lastname: Cianchi
authors.forename: Danilo
authors.initials: D
authors.lastname: Squatrito
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Emmi
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.forename: Domenico
authors.initials: D
authors.lastname: Prisco
authors.forename: Mario Milco
authors.initials: MM
authors.lastname: D'Elios
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001528:Behcet Syndrome / Q000097:blood / Q000276:immunology* / Q000628:therapy; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha