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

Objectives: CD4(+) CD25(high) regulatory T cells (T-REG) represent a suppressive T-cell subset that plays a key role in the modulation of immune responses and eventually in the prevention of autoimmunity. There is growing evidence that patients with autoimmune and inflammatory chronic diseases show an impairment of T-REG cells or activated effector T cells unresponsive to T-REG. Glucocorticoid-induced TNFR-related protein (GITR) is a widely accepted marker of murine T-REG cells, but little is known of its role in humans. The aim of the present study was to investigate the characteristics of different subsets of T-REG cells in Sjgren's syndrome and the potential role of GITR as a marker of human T-REG cells. Methods: Fifteen patients with primary Sjogren's syndrome (SS) and 10 sex-and age-matched normal controls (NC) were enrolled in the study. CD4(+) T cells were separated from peripheral blood by magnetic cell sorting (negative selection). Cell phenotype was analyzed by flow-cytometry using primary and secondary antibodies. Disease activity was assessed using the EULAR Sjgren's syndrome disease activity index (ESSDAI). Results: Although the proportion of circulating CD25(high)GITR(high) subset was similar in SS patients and normal controls, an expansion of the CD25(-)GITR(high) cell population was observed in the peripheral blood of SS patients. Interestingly, this expansion was greater in patients with inactive rather than active disease. Conclusions: The number of CD4(+) CD25(-)GITR(high) cells increases in SS as compared to normal controls. Furthermore, the fact that the expansion of this cell subset is mainly observed in patients with inactive disease suggests that these cells may play a role in counteracting inflammatory response.