OBJECTIVES: It has been recently observed that a T-cell subset, lacking of both CD4 and CD8 molecules and defined as double negative (DN), is expanded in the blood of patients with systemic lupus erythematosus, produces IL-17 and accumulates in the kidney during nephritis. Since IL-17 production is enhanced in salivary gland infiltrates of primary Sjögren's syndrome (SS) patients, we investigated whether DN T cells may be involved in the pathogenesis of salivary gland damage. METHODS: Phenotypic characterisation of peripheral blood mononuclear cells from SS patients and controls was performed by flow cytometry in freshly isolated and anti-CD3-stimulated cells. SS minor salivary glands were processed for immunofluorescence staining. RESULTS: CD3(+)CD4(-)CD8(-) DN T cells were major producers of IL-17 in SS and expressed ROR-γt. They were expanded in the peripheral blood, spontaneously produced IL-17 and infiltrated salivary glands. In addition, the expansion of αβ-TCR(+) DN T cells was associated with disease activity. Notably, IL-17-producing DN T cells from SS patients, but not from healthy controls, were strongly resistant to the in vitro effect of dexamethasone. CONCLUSIONS: These findings appear to be of great interest since the identification of a peculiar T-cell subset with pro-inflammatory activity, but resistant to corticosteroids, in an autoimmune disorder such as SS may help to design new specific treatments for the disease.
OBJECTIVES: It has been recently observed that a T-cell subset, lacking of both CD4 and CD8 molecules and defined as double negative (DN), is expanded in the blood of patients with systemic lupus erythematosus, produces IL-17 and accumulates in the kidney during nephritis. Since IL-17 production is enhanced in salivary gland infiltrates of primary Sjögren's syndrome (SS) patients, we investigated whether DN T cells may be involved in the pathogenesis of salivary gland damage. METHODS: Phenotypic characterisation of peripheral blood mononuclear cells from SS patients and controls was performed by flow cytometry in freshly isolated and anti-CD3-stimulated cells. SS minor salivary glands were processed for immunofluorescence staining. RESULTS: CD3(+)CD4(-)CD8(-) DN T cells were major producers of IL-17 in SS and expressed ROR-γt. They were expanded in the peripheral blood, spontaneously produced IL-17 and infiltrated salivary glands. In addition, the expansion of αβ-TCR(+) DN T cells was associated with disease activity. Notably, IL-17-producing DN T cells from SS patients, but not from healthy controls, were strongly resistant to the in vitro effect of dexamethasone. CONCLUSIONS: These findings appear to be of great interest since the identification of a peculiar T-cell subset with pro-inflammatory activity, but resistant to corticosteroids, in an autoimmune disorder such as SS may help to design new specific treatments for the disease.
Authors: Guillermo Carvajal Alegria; Pierre Gazeau; Sophie Hillion; Claire I Daïen; Divi Y K Cornec Journal: Clin Rev Allergy Immunol Date: 2017-10 Impact factor: 8.667
Authors: Niki M Moutsopoulos; Joanne Konkel; Mojgan Sarmadi; Mehmet A Eskan; Teresa Wild; Nicolas Dutzan; Loreto Abusleme; Camille Zenobia; Kavita B Hosur; Toshiharu Abe; Gulbu Uzel; Wanjun Chen; Triantafyllos Chavakis; Steven M Holland; George Hajishengallis Journal: Sci Transl Med Date: 2014-03-26 Impact factor: 17.956
Authors: Noé Rodríguez-Rodríguez; Giovanna Flores-Mendoza; Sokratis A Apostolidis; Florencia Rosetti; George C Tsokos; José C Crispín Journal: J Leukoc Biol Date: 2020-02-13 Impact factor: 4.962