IL-17-producing CD4-CD8- T cells are expanded in the peripheral blood, infiltrate salivary glands and are resistant to corticosteroids in patients with primary Sjogren's syndrome.

Alessia Alunno, Onelia Bistoni, Elena Bartoloni, Sara Caterbi, Barbara Bigerna, Alessia Tabarrini, Roberta Mannucci, Brunangelo Falini, Roberto Gerli

Rheumatology Unit, Department of Clinical & Experimental Medicine, University of Perugia, Via Enrico Dal Pozzo, Perugia I-06122, Italy. gerlir@unipg.it

Annals of the rheumatic diseases 2013 Feb

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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. 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. 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. 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.

Citation

Alessia Alunno, Onelia Bistoni, Elena Bartoloni, Sara Caterbi, Barbara Bigerna, Alessia Tabarrini, Roberta Mannucci, Brunangelo Falini, Roberto Gerli. IL-17-producing CD4-CD8- T cells are expanded in the peripheral blood, infiltrate salivary glands and are resistant to corticosteroids in patients with primary Sjogren's syndrome. Annals of the rheumatic diseases. 2013 Feb;72(2):286-92