Association of Graves' disease and prevalence of circulating IFN-gamma-producing CD28(-) T cells

Background Peripheral blood CD4(+) and CD8(+) T-cell subsets lacking surface CD28 have been suggested to predispose patients to immune-mediated disorders. Materials and Methods To determine the role of CD28(-) T-cell subset in Graves' disease (GD), we characterized peripheral blood CD4(+)CD28(-) and CD8(+)CD28(-) T cell from early onset GD patients. Results and Discussion GD patients had significantly higher percentages of CD4(+)CD28(-) and CD8(+)CD28(-) T cells than did healthy donors. Both CD28(-) T cells expressed mostly CD45RO, suggesting that they are activated and/or are memory T cells. GD patient-derived CD4(+)CD28(-) and CD8(+)CD28(-) T cells produced more intracellular IFN-gamma than their counterparts from healthy donors. Furthermore, CD4(+)CD28(-) and CD8(+)CD28(-) T cells from GD patients with Graves' ophthalmopathy (GO) secreted higher level of intracellular IFN-gamma than those CD28(-) T cells from GD patients without GO. Retrospective analysis showed that the increased levels of CD4(+)CD28(-) T cells and their IFN-gamma-producing subgroups were positively correlated to the serum anti-thyrotropin receptor (TSHR) autoantibodies (TRAb). Our observations suggest that increased IFN-gamma-producing CD28(-) T cells in GD patients may play an important role in the pathogenesis of GD.