Braley-Mullen H, Sharp G C, Kyriakos M
Department of Medicine, University of Missouri, Columbia 65212.
J Immunol. 1994 Jan 1;152(1):307-14.
Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTG transfer experimental autoimmune thyroiditis (EAT) in which the thyroid cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Addition of anti-IL2R antibody to cultures with MTg leads to activation of cells that induce granulomatous EAT, accompanied by high serum anti-MTg autoantibody responses, in recipient mice. CD4+ T cells are required to induce both forms of EAT; whether B cells and/or autoantibodies produced by MTg-sensitized B cells also contribute to disease severity or the type of thyroid histopathology is unknown. In our study, B cells and autoantibody responses produced in recipient mice were reduced either by column removal of B cells from donor spleen cells or by treatment of recipient mice with anti-I-AK mAb at the time of cell transfer. These maneuvers only slightly reduced the severity of lymphocytic EAT but markedly reduced the severity and incidence of granulomatous EAT developing in recipient mice. Delaying the initiation of anti-I-AK treatment until 6 days after cell transfer was less effective in reducing anti-MTg autoantibody responses or granulomatous EAT. These studies all suggested that anti-MTg autoantibodies were required for development of granulomatous but not lymphocytic EAT. However anti-I-AK-treated recipients receiving injections of anti-MTg antibody or having serum antibody induced by prior immunization with MTg and LPS also developed less severe granulomatous EAT than controls. These results suggest that sensitized CD4+ T cells and circulating anti-MTg autoantibody are not sufficient for development of granulomatous thyroid lesions. It is possible that antibodies having a unique function or specificity are produced in mice developing granulomatous EAT or thyroid-infiltrating B cells may directly contribute to the granulomatous inflammatory response.
用小鼠甲状腺球蛋白（MTg）体外激活的MTg致敏脾细胞可引发实验性自身免疫性甲状腺炎（EAT），其中甲状腺细胞浸润主要由单核细胞组成（淋巴细胞性EAT）。在含有MTg的培养物中添加抗IL2R抗体可导致细胞活化，从而在受体小鼠中诱导肉芽肿性EAT，并伴有高血清抗MTg自身抗体反应。诱导两种形式的EAT均需要CD4 + T细胞；MTg致敏的B细胞产生的B细胞和/或自身抗体是否也会影响疾病严重程度或甲状腺组织病理学类型尚不清楚。在我们的研究中，通过从供体脾细胞中柱式去除B细胞或在细胞转移时用抗I-AK单克隆抗体治疗受体小鼠，可降低受体小鼠中产生的B细胞和自身抗体反应。这些操作仅略微降低了淋巴细胞性EAT的严重程度，但显著降低了受体小鼠中肉芽肿性EAT的严重程度和发生率。将抗I-AK治疗的起始时间推迟到细胞转移后6天，在降低抗MTg自身抗体反应或肉芽肿性EAT方面效果较差。这些研究均表明，抗MTg自身抗体是肉芽肿性EAT而非淋巴细胞性EAT发展所必需的。然而，接受抗MTg抗体注射或具有先前用MTg和LPS免疫诱导的血清抗体的抗I-AK治疗的受体，其肉芽肿性EAT的严重程度也低于对照组。这些结果表明，致敏的CD4 + T细胞和循环抗MTg自身抗体不足以形成肉芽肿性甲状腺病变。有可能在发生肉芽肿性EAT的小鼠中产生具有独特功能或特异性的抗体，或者甲状腺浸润性B细胞可能直接促成肉芽肿性炎症反应。
