Aberrant GITR expression on different T cell subsets and the regulation by glucocorticoid in systemic lupus erythematosus.

International journal of rheumatic diseases

PubMedID: 25293713

Sun J, Yu N, Li X, Wang L, Pan Y, Li X, Tao J, Chen Z, Wang G. Aberrant GITR expression on different T cell subsets and the regulation by glucocorticoid in systemic lupus erythematosus. Int J Rheum Dis. 2014;.
AIM
The dysfunction of T regulatory cells is important for the pathogenesis of systemic lupus erythematosus (SLE). Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed at low levels on resting responder T lymphocytes (Tresps) and is up-regulated on T regulatory cells (Tregs) and activated T cells, diminishing suppressive activity of Tregs and/or leading to resistance to suppression of Tregs by activated effector T cells. We aimed to explore whether SLE patients had an aberrant expression of GITR on Tregs and responder T cells (Tresps) and the regulation by glucocorticoids.

METHODS
The surface GITR expression on Tregs and Tresps cells were analyzed by flow cytometry in 32 patients and 15 normal controls. Purified Tregs or Tresps were cultured with glucocorticoid. Apoptosis of the cells were determined by the staining of Annexin V.

RESULTS
Systemic lupus erythematosus patients had higher levels of GITR expressed on CD4(+) CD25(+) , CD4(+) CD25(high) and CD4(+) CD25(+) CD127(low/-) Tregs as well as on CD4(+) CD25(-) Tresps compared to healthy controls. The expression of GITR on Tregs and Tresps were positively correlated with score of SLE disease activity index (SLEDAI). In vitro glucocorticoid induced GITR expression on purified Tresp cells, but not on Tregs, and almost all of the GITR positive cells induced by glucocorticoid encountered apoptosis.

CONCLUSION
Aberrant expression of GITR may contribute to SLE pathogenesis. Glucocorticoid may achieve its therapeutic effect partly by inducing GITR expression on Tresps rather than Tregs, which initiates the apoptosis of Tresp cells in SLE patients.