Gessl A, Waldhäusl W
Department of Medicine III, University of Vienna, Austria.
Clin Immunol Immunopathol. 1998 May;87(2):168-75. doi: 10.1006/clin.1998.4524.
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.
本研究采用三色流式细胞术，调查了自身免疫性甲状腺炎患者（AT，N = 28）或未经治疗的甲状腺功能亢进型格雷夫斯病患者（GDH，N = 34）外周血中初始（CD45RA +）和记忆（CD45RA -）CD4 +以及CD8 + T细胞中的T细胞活化标志物HLA - DR和CD69。结果表明，与健康受试者（HS，N = 26）相比，AT患者而非GDH患者的总CD4 +细胞（AT：14.1%；GDH：11.3%；HS：10.9%）、CD8 +细胞（AT：31.9%；GDH：23.5%；HS：19.4%）以及CD45RA - CD4 +细胞（AT：11.2%；GDH：7.7%；HS：7.9%）上HLA - DR抗原表达量增加。在GDH（+71%）和AT（+91%）中，仅HLA - DR + CD45RA + CD8 +细胞的比例相对于HS有所增加。此外，接受甲巯咪唑治疗的甲状腺功能正常的GD患者（GDE，N = 22）在总CD4 +细胞（分别为+37%和40%）和CD8 +细胞（分别为+47%和93%）以及CD45RA -细胞中的HLA - DR +表达均高于GDH。此外，相对于HS，总CD4 +细胞、CD45RA + CD4 +细胞和CD8 +细胞均有所增加。相比之下，AT和GDH患者总CD4 +细胞（分别为+97%和74%）和CD8 +细胞（分别为+95%和68%）及其所有亚群（GDH中的CD45RA -细胞除外）上CD69阳性T细胞的比例增加，但在进行抗甲状腺药物治疗后恢复正常。我们得出结论，自身免疫性甲状腺疾病患者中，（a）HLA - DR + CD45RA + CD8 + T细胞与HS相比比例几乎高出两倍，（b）总CD4 +和CD8 +细胞上的CD69比例更高，在AT和未经治疗的GD患者的CD45RA +亚群中升高更为明显。此外，（c）GD患者接受甲巯咪唑抗甲状腺药物治疗后，循环中的HLA - DR + CD4 +和CD8 +细胞及其CD45RA -亚群进一步增加，但CD69表达降低。这些数据表明HLA - DR表达与持续的自身免疫有关，而CD69表达增加部分也与GDH中甲状腺激素浓度升高有关。
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