Matsunaga M, Eguchi K, Fukuda T, Kurata A, Tezuka H, Shimomura C, Otsubo T, Ishikawa N, Ito K, Nagataki S
J Clin Endocrinol Metab. 1986 Apr;62(4):723-8. doi: 10.1210/jcem-62-4-723.
Class II major histocompatibility complex (MHC) antigens have been demonstrated on the surface of thyroid epithelial cells (thyrocytes) from patients with autoimmune thyroid disease. The present study was designed to investigate how the expression of class II MHC antigens is involved in autoimmune processes in Graves' disease by studying cellular interactions among thyrocytes, lymphocytes within thyroid glands (TG), and peripheral blood (PB) lymphocytes. Thyrocytes were prepared by collagenase digestion, and T or non-T cells were separated by E-rosette formation. Thyrocytes were cocultured in the presence or absence of interferon-gamma, and the expression of HLA-DR antigens on cultured thyrocytes was examined by an indirect immunofluorescence method using monoclonal anti-HLA-DR antibody and monoclonal anti-HLA-DQ antibody. The cellular interactions were assessed as the proliferative response of T cells to autologous stimulators, such as thyrocytes or lymphocytes. Expression of HLA-DR antigens on thyrocytes after culture for 18 h in the absence of interferon-gamma was found in two thirds of the patients with Graves' disease studied (n = 18). Interferon-gamma induced and maintained the expression of HLA-DR antigens on thyrocytes. The percentages of HLA-DR+T cells were significantly higher among TG-T cells than among PB-T cells [32.6 +/- 12.4% (+/- SD) vs. 12.2 +/-5.0%; n = 18; P less than 0.01]. Thyrocytes from Graves' patients induced proliferation of both autologous PB-T cells and TG-T cells, and TG-T cells stimulated proliferation of autologous PB-T cells. In conclusion, interferon-gamma induces HLA-DR antigen expression on thyrocytes from patients with Graves' disease, and these cells induce proliferation of autologous T cells, which may, in turn, act on thyrocytes to perpetuate the process.
II类主要组织相容性复合体（MHC）抗原已在自身免疫性甲状腺疾病患者的甲状腺上皮细胞（甲状腺细胞）表面得到证实。本研究旨在通过研究甲状腺细胞、甲状腺内淋巴细胞（TG）和外周血（PB）淋巴细胞之间的细胞相互作用，探讨II类MHC抗原的表达如何参与格雷夫斯病的自身免疫过程。通过胶原酶消化制备甲状腺细胞，并通过E花环形成分离T细胞或非T细胞。甲状腺细胞在有或无γ干扰素的情况下共培养，使用单克隆抗HLA-DR抗体和单克隆抗HLA-DQ抗体，通过间接免疫荧光法检测培养的甲状腺细胞上HLA-DR抗原的表达。细胞相互作用通过T细胞对自体刺激物（如甲状腺细胞或淋巴细胞）的增殖反应来评估。在研究的三分之二格雷夫斯病患者（n = 18）中，发现甲状腺细胞在无γ干扰素的情况下培养18小时后表达HLA-DR抗原。γ干扰素诱导并维持甲状腺细胞上HLA-DR抗原的表达。TG-T细胞中HLA-DR+T细胞的百分比显著高于PB-T细胞[32.6 +/- 12.4%（+/-标准差）对12.2 +/- 5.0%；n = 18；P < 0.01]。格雷夫斯病患者的甲状腺细胞诱导自体PB-T细胞和TG-T细胞增殖，并且TG-T细胞刺激自体PB-T细胞增殖。总之，γ干扰素诱导格雷夫斯病患者甲状腺细胞上HLA-DR抗原表达，并且这些细胞诱导自体T细胞增殖，而自体T细胞反过来可能作用于甲状腺细胞使该过程持续下去。
