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.
OBJECTIVE
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.
Rheumatology Unit, Department of Clinical & Experimental Medicine, University of Perugia, Via Enrico Dal Pozzo, Perugia I-06122, Italy. gerlir@unipg.it
Alessia
A
Alunno
Onelia
O
Bistoni
Elena
E
Bartoloni
Sara
S
Caterbi
Barbara
B
Bigerna
Alessia
A
Tabarrini
Roberta
R
Mannucci
Brunangelo
B
Falini
Roberto
R
Gerli
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008875:Middle Aged; D012469:Salivary Glands / Q000276:immunology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D020381:Interleukin-17; D003907:Dexamethasone