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Journal of Immunology Research
Volume 2015, Article ID 171520, 17 pages
Review Article

Glucocorticoid-Induced Tumour Necrosis Factor Receptor-Related Protein: A Key Marker of Functional Regulatory T Cells

Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy

Received 8 January 2015; Accepted 18 March 2015

Academic Editor: Xiao-Feng Yang

Copyright © 2015 Simona Ronchetti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR, TNFRSF18, and CD357) is expressed at high levels in activated T cells and regulatory T cells (Tregs). In this review, we present data from mouse and human studies suggesting that GITR is a crucial player in the differentiation of thymic Tregs (tTregs), and expansion of both tTregs and peripheral Tregs (pTregs). The role of GITR in Treg expansion is confirmed by the association of GITR expression with markers of memory T cells. In this context, it is not surprising that GITR appears to be a marker of active Tregs, as suggested by the association of GITR expression with other markers of Treg activation or cytokines with suppressive activity (e.g., IL-10 and TGF-), the presence of GITR+ cells in tissues where Tregs are active (e.g., solid tumours), or functional studies on Tregs. Furthermore, some Treg subsets including Tr1 cells express either low or no classical Treg markers (e.g., FoxP3 and CD25) and do express GITR. Therefore, when evaluating changes in the number of Tregs in human diseases, GITR expression must be evaluated. Moreover, GITR should be considered as a marker for isolating Tregs.