Glucocorticoid induced TNFR-related protein (GITR) as marker of human regulatory T cells: expansion of the GITR+CD25- cell subset in patients with systemic lupus erythematosus

Abstract

Objectives: Regulatory T cells (T REG) represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR) is a well known marker of murine T REG cells, but little is known in humans. The aim of this study was to investigate the characteristics of T REG cells in systemic lupus erythematosus (SLE) and the potential role of GITR as marker of human T REG. Methods: Nineteen SLE patients and 15 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 and real time polymerase-chain reaction (PCR) using TaqMan probes. Results: The CD25 highGITR high subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05). On the opposite, the CD25 -GITR high cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01). Interestingly, FoxP3 at mRNA level was expressed in both CD25 - GITR high and CD25 highGITR high cells, suggesting that both cell subsets have regulatory activity. Conclusions: CD4 +CD25 -GITR high cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset.