Background: Gastrointestinal involvement is one of the most serious in Behcet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behcet 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-gamma and TNF-alpha, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-gamma 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-alpha, 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-alpha agents and suggest the use of anti-IL-17 monoclonal antibodies in Behcet patients with early intestinal involvement.

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 / Emmi, Giacomo; Silvestri, Elena; Bella, Chiara Della; Grassi, Alessia; Benagiano, Marisa; Cianchi, Fabio; Squatrito, Danilo; Cantarini, Luca; Emmi, Lorenzo; Selmi, Carlo; Prisco, Domenico; D'Elios, Mario Milco. - In: MEDICINE. - ISSN 1536-5964. - ELETTRONICO. - 95:(2016), pp. e5516-e5521. [10.1097/MD.0000000000005516]

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

Emmi, Giacomo;Silvestri, Elena;Bella, Chiara Della;Grassi, Alessia;Benagiano, Marisa;Cianchi, Fabio;Squatrito, Danilo;Emmi, Lorenzo;Prisco, Domenico;D'Elios, Mario Milco
2016

Abstract

Background: Gastrointestinal involvement is one of the most serious in Behcet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behcet 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-gamma and TNF-alpha, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-gamma 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-alpha, 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-alpha agents and suggest the use of anti-IL-17 monoclonal antibodies in Behcet patients with early intestinal involvement.
2016
95
e5516
e5521
Goal 3: Good health and well-being
Emmi, Giacomo; Silvestri, Elena; Bella, Chiara Della; Grassi, Alessia; Benagiano, Marisa; Cianchi, Fabio; Squatrito, Danilo; Cantarini, Luca; Emmi, Lorenzo; Selmi, Carlo; Prisco, Domenico; D'Elios, Mario Milco
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1355274
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