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自身免疫性甲状腺疾病中针对甲状腺细胞膜抗原的细胞免疫反应模式及特异性免疫调节缺陷

Patterns of cellular immune responses to thyrocyte membrane antigens and specific immunoregulatory defects in autoimmune thyroid disease.

作者信息

O'Brien C J, Macchia E, Cundy T F, Concetti R, McSorley C G, MacFarlane I G, Vento S, Eddleston A L

机构信息

Liver Unit, King's College School of Medicine and Dentistry, London, U.K.

出版信息

J Clin Lab Immunol. 1990 Jul;32(3):103-8.

PMID:1966945
Abstract

Although Graves' disease (GD), Hashimoto's thyroiditis (HT) and idiopathic myxoedema (Myx) are clinically distinct autoimmune thyroid diseases, previous studies using crude thyroid preparations as a source of antigens have failed to identify differences in cellular immune responses. In this study, we have assessed cellular immunity in patients with these disorders to two antigen preparations (derived from thyroid gland and cervical fat) enriched in cell membranes and known to share a functional TSH receptor. Using an indirect T-lymphocyte migration inhibitory factor (T-LIF) assay, T-cell immunity to thyroid membranes was demonstrated in 11/11 patients with GD, 4/5 with HT and 4/5 with Myx, but in none of 18 patients with chronic active hepatitis (another organ-specific autoimmune disease) or sixteen healthy controls. In contrast, T lymphocytes responsive to adipocyte membranes were detected only in patients with GD. TSH binding inhibiting antibodies were found exclusively in six patients with GD, and thyroid stimulating antibodies in five of these patients. In co-culture experiments designed to study the activity of antigen-specific suppressor T cells, low numbers of T cells from 6/6 normal controls, 4/4 patients with HT and 5/5 patients with myxoedema suppressed the response to adipocyte membranes of T lymphocytes from patients with Graves' disease. The results of this study demonstrate different patterns of T-cell reactivity to thyroid antigens in patients with Graves' disease, Hashimoto's thyroiditis and myxoedema and suggest that cellular immunity to the TSH receptor is restricted to patients with Graves' disease and associated with a defect in the specific immunoregulatory control of this response.

摘要

尽管格雷夫斯病(GD)、桥本甲状腺炎(HT)和特发性黏液性水肿(Myx)在临床上是不同的自身免疫性甲状腺疾病,但以往使用粗制甲状腺制剂作为抗原来源的研究未能识别出细胞免疫反应的差异。在本研究中,我们评估了患有这些疾病的患者对两种富含细胞膜且已知共享功能性促甲状腺激素(TSH)受体的抗原制剂(源自甲状腺和颈部脂肪)的细胞免疫。使用间接T淋巴细胞迁移抑制因子(T-LIF)测定法,在11例GD患者中的11例、5例HT患者中的4例和5例Myx患者中的4例中证实了对甲状腺膜的T细胞免疫,但在18例慢性活动性肝炎患者(另一种器官特异性自身免疫性疾病)或16名健康对照中均未发现。相比之下,仅在GD患者中检测到对脂肪细胞膜有反应的T淋巴细胞。促甲状腺激素结合抑制抗体仅在6例GD患者中发现,其中5例患者存在甲状腺刺激抗体。在旨在研究抗原特异性抑制性T细胞活性的共培养实验中,6例正常对照中的6例、4例HT患者中的4例和5例黏液性水肿患者中的5例的少量T细胞抑制了格雷夫斯病患者T淋巴细胞对脂肪细胞膜的反应。本研究结果表明,格雷夫斯病、桥本甲状腺炎和黏液性水肿患者对甲状腺抗原的T细胞反应模式不同,并表明对TSH受体的细胞免疫仅限于格雷夫斯病患者,且与该反应的特异性免疫调节控制缺陷有关。

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