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.
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.
Gessl
A
A
Department of Medicine III, University of Vienna, Austria. alois.gessl@akh-wien.ac.at
Waldhäusl
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W
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D013956:Antithyroid Agents / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D008875:Middle Aged; D013959:Thyroid Diseases / Q000097:blood* / Q000188:drug therapy; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D013956:Antithyroid Agents; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D008713:Methimazole; D000099192:CD69 Antigens