Immunopathology of primary hypophysitis -: Implications for pathogenesis
Immunopathology of primary hypophysitis -: Implications for pathogenesis
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DOI：
10.1097/01.pas.0000149707.12335.8e
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发表时间：
2005-03-01
影响因子：
5.6
通讯作者：
Brück, W
中科院分区：
文献类型：
--
作者：
Gutenberg, A;Buslei, R;Brück, W
原发性垂体炎的病因尚未完全阐明。组织学上，原发性垂体炎包括三种不同的主要亚型：淋巴细胞性（LYH）、肉芽肿性（GRH）和黄色瘤性（XH）垂体炎。临床和实验室结果提示原发性垂体炎的自身免疫基础。关于炎性浸润的组成和相关的免疫病理效应机制仍存在争议。因此，21例原发性垂体炎的不同亚型进行了分析，淋巴细胞和巨噬细胞抗原的表达，以及MHC I类和II类分子的炎症浸润和居民垂体腺泡细胞。LYH（n = 15）、GRH（n = 4）和XH（n = 2）的淋巴细胞浸润主要由T细胞组成，而B细胞很少。独立于组织病理学亚型，T细胞亚群显示出相等的CD4+与CD8+ T细胞的比例。最高数量的活化的CD8+ T细胞观察LYH在怀孕期间，周围甚至浸润保存的垂体腺泡细胞。此外，活化的CD8+ T细胞的比率增加与临床症状的持续时间较短相关。在LYH中，观察到垂体细胞上的MHC IT类抗原的异常表达以及MHC I类分子的过表达。独立的组织学亚型，巨噬细胞主要表达慢性活化的标志物，并显示MHC II类阳性。LYH、GRH和XH虽然在组织学外观和年龄分布上具有异质性，但即使不完全相同，也表现出相似的免疫组织学特征。在CD4+ T细胞的初始帮助下，通过CD8+ T细胞的直接T细胞介导的细胞毒性很可能在原发性垂体炎的发病机制中起关键作用，涉及垂体细胞表达的靶自身抗原。
The etiology of primary hypophysitis is still not fully elucidated. Histologically, primary hypophysitis includes three different main subtypes: lymphocytic (LYH), granulomatous (GRH), and xanthomatous (XH) hypophysitis. Clinical and laboratory findings suggest an autoimmune basis in primary hypophysitis. Controversy still exists about the composition of the inflammatory infiltrate and the relevant immunopathogenic effector mechanisms. Therefore, 21 cases of primary hypophysitis of different subtypes were analyzed with respect to the expression of lymphocyte and macrophage antigens as well as MHC class I and II molecules of the inflammatory infiltrate and the resident pituitary acinar cells. Lymphocyte infiltration in LYH (n = 15), but also in GRH (n = 4) and XH (n = 2), mainly consisted of T cells, while B cells were rare. Independent from the histopathologic subtype, T cell subsets showed equal ratios of CD4+ to CD8+ T cells. Highest numbers of activated CD8+ T cells were observed in LYH presenting during pregnancy, surrounding or even infiltrating preserved pituitary acinar cells. Moreover, an increased rate of activated CD8+ T cells correlated with a shorter duration of clinical symptoms. In LYH, aberrant expression of MHC class IT antigens as well as overexpression of MHC class I molecules on pituitary cells were observed. Independent of the histologic subtype, macrophages mostly expressed markers of chronic activation and showed MHC class II positivity. LYH, GRH, and XH, although heterogeneous in their histologic appearance and in age distribution, exhibit a similar if not identical immunohistologic profile. It is highly likely that direct T cell-mediated cytotoxicity through CD8+ T cells, with the initial help of CD4+ T cells, is pivotal in the pathogenesis of primary hypophysitis, implicating a target autoantigen expressed by pituitary cells.