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IL-17-producing CD4CD8 T cells are expanded in the peripheral blood, infiltrate salivary glands and are resistant to corticosteroids in patients with primary Sjögren's syndrome
  1. Alessia Alunno1,
  2. Onelia Bistoni1,
  3. Elena Bartoloni1,
  4. Sara Caterbi1,
  5. Barbara Bigerna2,
  6. Alessia Tabarrini2,
  7. Roberta Mannucci3,
  8. Brunangelo Falini2,
  9. Roberto Gerli1
  1. 1Rheumatology Unit, Department of Clinical & Experimental Medicine, University of Perugia, Perugia, Italy
  2. 2Department of Clinical & Experimental Medicine, Institute of Hematology, University of Perugia, Perugia, Italy
  3. 3Laboratory of Confocal Microscopy and Image Analysis, University of Perugia, Perugia, Italy
  1. Correspondence to Professor Roberto Gerli, Rheumatology Unit, Department of Clinical & Experimental Medicine, University of Perugia, Via Enrico Dal Pozzo, Perugia I-06122, Italy; gerlir{at}unipg.it

Abstract

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+CD4CD8 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.

  • Sjögren's Syndrome
  • T Cells
  • Corticosteroids

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