Objective: We investigated longitudinal changes in circulating CD4 + and CD8 + T cells positive for programed cell death protein-1 (PD-1) and in other subsets of CD4 + T cells in untreated hyperthyroid patients with Graves' disease after treatment with methimazole (MMI).Design and Patients: The study included 18 untreated hyperthyroid patients with Graves' disease and 18 age-matched controls. Before and after 12-week treatment with MMI, we used flow cytometry to measure circulating PD-1 + D4 + and PD-1 + CD8+ T cells and subsets of CD4 + T cells in peripheral blood, as well as serum levels of chemokines related to T-helper type 1 (Th-1) and Th-2 cells.Results: At baseline, the percentage of CD4 + and CD8 + T cells expressing PD-1 was significantly higher in patients than in age-matched controls. Serum levels of chemokines related to Th-1 and Th-2 also were higher in patients. Twelve weeks after initiation of MMI, the percentage of CD4 + T cells expressing PD-1 was significantly lower than at baseline, but no such change was seen in CD8 + T cells.Furthermore, the percentage of Th-1 cells among CD4 + T cells and the serum levels of soluble CD26/dipeptidyl peptidase-4, a surface marker of Th-1 cells, also were significantly lower than at baseline.
Conclusions:The expression of PD-1 on circulating CD4 + and CD8 + T cells is increased in hyperthyroid patients with active Graves' disease. MMI significantly decreases levels of circulating PD-1 + CD4 + T cells, suggesting that PD-1 + T lymphocytes may be associated with the pathogenesis of Graves' disease.
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