Elevated CD69 expression on naive peripheral blood T-cells in hyperthyroid Graves' disease and autoimmune thyroiditis: discordant effect of methimazole on HLA-DR and CD69

Abstract

This study investigated T-cell activation markers HLA-DR and CD69 in both naive (CD45RA+) and memory (CD45RA-) CD4+ as well as CD8+ T cells in peripheral blood of patients with autoimmune thyroiditis (AT, N = 28) or hyperthyroid untreated Graves' disease (GDH, N = 34) using three-color flow cytometry. It was demonstrated that patients with AT, but not those with GDH, expressed increased amounts of HLA-DR antigen compared to healthy subjects (HS, N = 26) on total CD4+ (AT: 14.1%; GDH: 11.3%; HS: 10.9%) and CD8+ cells (AT: 31.9%; GDH: 23.5%; HS: 19.4%) as well as on CD45RA- CD4+ cells (AT: 11.2%; GDH: 7.7%; HS: 7.9%). In GDH (+71%) and AT (+91%) only the proportion of HLA-DR+ CD45RA+ CD8+ cells was increased vs HS. Furthermore, euthyroid GD patients on methimazole (GDE, N = 22) displayed greater HLA-DR+ expression on total and CD45RA- cells within both CD4+ (+37 and 40%, respectively) and CD8+ cells (+47 and 93%, respectively) than GDH. In addition, total and CD45RA+ CD4+ and CD8+ cells were increased vs HS. In contrast, proportions of CD69 positive T cells were increased in AT and GDH on total CD4+ (+97 and 74%, respectively) and CD8+ (+95 and 68%, respectively) cells and all subsets thereof (except for CD45RA- cells in GDH), but normalized upon thyrostatic treatment. We conclude that patients with autoimmune thyroid disease harbor an almost twofold greater proportion vs HS of (a) HLA-DR+ CD45RA+ CD8+ T cells, and of (b) CD69 on total CD4+ and CD8+ cells, and an even more marked elevation on their CD45RA+ subset in AT and untreated GD. In addition, (c) thyrostatic treatment by methimazole in GD is accompanied by a further increase in circulating HLA-DR+ CD4+ and CD8+ cells and their CD45RA- subsets, but decreased CD69 expression. These data suggest association of HLA-DR expression with ongoing autoimmunity, while increased CD69 expression relates in part also to elevated thyroid hormone concentration in GDH.