Effects of treatment with methimazole on circulating CD4+ and CD8+ T cells positive for programed cell death protein-1 and on subsets of CD4+ T cells in untreated hyperthyroid patients with Graves' disease

Abstract

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.

Keywords: CD4; CD8; Graves' disease; PD-1; Th-1 cells; hyperthyroidism; methimazole.