{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:36:28Z","timestamp":1789140988386,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated longitudinal changes in circulating CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u00a0cells positive for programed cell death protein\u20101 (PD\u20101) and in other subsets of CD4<jats:sup>+<\/jats:sup> T\u00a0cells in untreated hyperthyroid patients with Graves' disease after treatment with methimazole (MMI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Patients<\/jats:title><jats:p>The study included 18 untreated hyperthyroid patients with Graves' disease and 18 age\u2010matched controls. Before and after 12\u2010week treatment with MMI, we used flow cytometry to measure circulating PD\u20101<jats:sup>+<\/jats:sup>\u00a0D4<jats:sup>+<\/jats:sup> and PD\u20101<jats:sup>+<\/jats:sup> CD8+ T\u00a0cells and subsets of CD4<jats:sup>+<\/jats:sup> T\u00a0cells in peripheral blood, as well as serum levels of chemokines related to T\u2010helper type 1 (Th\u20101) and Th\u20102 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, the percentage of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u00a0cells expressing PD\u20101 was significantly higher in patients than in age\u2010matched controls. Serum levels of chemokines related to Th\u20101 and Th\u20102 also were higher in patients. Twelve weeks after initiation of MMI, the percentage of CD4<jats:sup>+<\/jats:sup> T\u00a0cells expressing PD\u20101 was significantly lower than at baseline, but no such change was seen in CD8<jats:sup>+<\/jats:sup> T\u00a0cells. Furthermore, the percentage of Th\u20101 cells among CD4<jats:sup>+<\/jats:sup> T\u00a0cells and the serum levels of soluble CD26\/dipeptidyl peptidase\u20104, a surface marker of Th\u20101 cells, also were significantly lower than at baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The expression of PD\u20101 on circulating CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u00a0cells is increased in hyperthyroid patients with active Graves' disease. MMI significantly decreases levels of circulating PD\u20101<jats:sup>+<\/jats:sup>\u00a0CD4<jats:sup>+<\/jats:sup> T\u00a0cells, suggesting that PD\u20101<jats:sup>+<\/jats:sup> T\u00a0lymphocytes may be associated with the pathogenesis of Graves' disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14788","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T05:35:52Z","timestamp":1655098552000},"page":"841-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of treatment with methimazole on circulating CD4<sup>+<\/sup> and CD8<sup>+<\/sup> T\u00a0cells positive for programed cell death protein\u20101 and on subsets of CD4<sup>+<\/sup> T\u00a0cells in untreated hyperthyroid patients with Graves' disease"],"prefix":"10.1111","volume":"97","author":[{"given":"Nanako","family":"Hirao","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Dokkyo 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