Expansion of CD4+CD25-GITR+ regulatory T-cell subset in the peripheral blood of patients with primary Sjögren's syndrome: correlation with disease activity

Reumatismo. 2012 Dec 11;64(5):293-8. doi: 10.4081/reumatismo.2012.293.


Objectives: CD4+CD25high regulatory T cells (TREG) represent a suppressive T cell subset deeply involved in the modulation of immune responses and eventually in the prevention of autoimmunity. Growing evidence demonstrated that patients with autoimmune and inflammatory chronic diseases display an impairment of TREG cells or activated effector T cells unresponsive to TREG. Glucocorticoid-induced TNFR-related protein (GITR) is a widely accepted marker of murine TREG cells, but little is known in humans. Aim of the present study was to investigate the characteristics of different subsets of TREG cells in Sjögren's syndrome and the potential role of GITR as marker of human TREG cells.

Methods: Fifteen patients with primary Sjogren's syndrome (SS) and 10 sex- and age-matched normal controls (NC) were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies. Disease activity was assessed using the EULAR Sjögren's syndrome disease activity index (ESSDAI).

Results: Although the proportion of circulating CD25highGITRhigh subset was similar in SS patients and NC, an expansion of the CD25-GITRhigh cell population was observed in the peripheral blood of SS patients. Interestingly, this expansion was more relevant in patients with inactive rather than active disease.

Conclusions: The number of CD4+CD25-GITRhigh cells is increased in SS as compared to NC. Moreover, the fact that the expansion of this cell subset is prevalently observed in patients with inactive disease suggests that these cells may play a role in counteracting inflammatory response.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • CD4 Antigens / analysis
  • Case-Control Studies
  • Disease Models, Animal
  • Female
  • Glucocorticoid-Induced TNFR-Related Protein / analysis
  • Humans
  • Immunophenotyping
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Lymphocyte Count
  • Middle Aged
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • CD4 Antigens
  • Glucocorticoid-Induced TNFR-Related Protein
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • TNFRSF18 protein, human