IL-17-producing double-negative T cells are expanded in the peripheral blood, infiltrate the salivary gland and are partially resistant to corticosteroid therapy in patients with Sjögren’s syndrome

  • A. Alunno S.S.D. di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Italy.
  • O. Bistoni S.S.D. di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Italy.
  • E. Bartoloni Bocci S.S.D. di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Italy.
  • S. Caterbi S.S.D. di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Italy.
  • B. Bigerna Sezione di Ematologia con TMO Università degli Studi di Perugia, Italy.
  • A. Pucciarini Sezione di Ematologia con TMO Università degli Studi di Perugia, Italy.
  • A. Tabarrini Sezione di Ematologia con TMO Università degli Studi di Perugia, Italy.
  • R. Mannucci Laboratorio di Microscopia Confocale ed Analisi d’Immagine, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Italy.
  • D. Beghelli Dipartimento di Scienze Ambientali, Università di Camerino, Italy.
  • B. Falini Sezione di Ematologia con TMO Università degli Studi di Perugia, Italy.
  • R. Gerli | gerlir@unipg.it S.S.D. di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Italy.

Abstract

A small CD3+ T-cell population, that lacks both CD4 and CD8 molecules, defined as double negative (DN), is expanded in the peripheral blood of patients with systemic lupus erythematosus, produces IL-17 and accumulates in the kidney during lupus nephritis. Since IL-17 production is enhanced in salivary gland infiltrates of patients with primary Sjögren’s syndrome (pSS), we aimed to investigate whether DN T cells may be involved in the pathogenesis of salivary gland damage. Fifteen patients with SS and 15 normal controls (NC) were enrolled. Peripheral blood mononuclear cells were stimulated with anti-CD3 antibody and cultured in presence or absence of dexamethasone (Dex). Phenotypic characterization was performed by flow cytometry in freshly isolated cells and after culture. Minor salivary glands (MSG) from pSS were processed for immunofluorescence staining. Total circulating DN T cells were increased in pSS compared to NC (4.7±0.4% vs 2.6±0.4%). NC and pSS freshly isolated DN T cells produce consistent amounts of IL-17 (67.7±5.6 in NC vs 69.2±3.3 in pSS). Notably, DN T cells were found in the pSS-MSG infiltrate. Dex was able to down-regulate IL-17 in vitro production in NC (29±2.6% vs 15.2±1.9% vs 13±1.6%) and pSS (49±4.8% vs 16±3.8% vs 10.2±0.8%) conventional Th17 cells and in DN T cells of NC (80±2.8% vs 3.8±2.1% vs 4.2±1.8%), but not of pSS (81±1.5% vs 85.4±0.8% vs 86.2±1.7%). DN T cells are expanded in pSS PB, produce IL-17 and infiltrate pSS MSG. In pSS, conventional Th17 cells are inhibited by Dex, but DN T cells appear to be resistant to this effect. Taken together, these data suggest a key role of this T-cell subset in the perpetuation of chronic sialoadenitis and eventually in pSS prognosis.

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Published
2013-10-31
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Keywords:
T helper 17 cells, Sjögren’s syndrome, dexamethasone.
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How to Cite
Alunno, A., Bistoni, O., Bartoloni Bocci, E., Caterbi, S., Bigerna, B., Pucciarini, A., Tabarrini, A., Mannucci, R., Beghelli, D., Falini, B., & Gerli, R. (2013). IL-17-producing double-negative T cells are expanded in the peripheral blood, infiltrate the salivary gland and are partially resistant to corticosteroid therapy in patients with Sjögren’s syndrome. Reumatismo, 65(4), 192-198. https://doi.org/10.4081/reumatismo.2013.192