CD4(-)CD8(-) T-cells in primary Sjögren's syndrome: association with the extent of glandular involvement

J Autoimmun. 2014 Jun;51:38-43. doi: 10.1016/j.jaut.2014.01.030. Epub 2014 Jan 24.

Abstract

Objectives: Growing evidence suggests that IL-17-producing T cells, lacking both CD4 and CD8 molecules and defined as double negative (DN) cells, play a pivotal role in the pathogenesis of a number of systemic autoimmune disorders. We recently demonstrated that this T-cell subset is expanded in the peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS), produces IL-17 and accumulates in minor salivary glands (MSGs). We aimed to investigate glandular and PB DN T cells in early pSS in order to verify a possible correlation with MSGs histological patterns and clinical parameters.

Methods: Paired samples of PB mononuclear cells and MSGs from pSS patients were evaluated at the diagnosis by flow cytometry and immunofluorescence staining respectively. Histological analysis to identify histological scores, B/T cell segregation and the presence of germinal center (GC)-like structures was also performed.

Results: In early stages of pSS, circulating DN T cells appear to be not yet expanded and inversely correlated with circulating CD4(+)Th17 cells. The number of infiltrating DN T cells were associated with extent of glandular involvement, presence of GC-like structures and dryness symptoms and were inversely correlated with circulating DN T cells.

Conclusions: Our findings suggest that DN T cells are actively involved in the pathogenic mechanisms leading to glandular dysfunction and damage in pSS and may play a role in ectopic lymphoneogenesis development occurring during the disease.

Keywords: Double negative T cells; Minor salivary gland biopsy; Sjogren's syndrome; Th17 cells.

MeSH terms

  • Adult
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Salivary Glands, Minor / immunology*
  • Salivary Glands, Minor / pathology*
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / metabolism
  • Sjogren's Syndrome / pathology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • CD4 Antigens
  • CD8 Antigens